METHODS OF USING GENETIC MARKERS ASSOCIATED WITH ENDOMETRIOSIS

Abstract

Disclosed herein are methods of using genetic markers associated with endometriosis, for example via a computer-implemented program to predict risk of developing endometriosis, and methods of preventing or treating endometriosis or a symptom thereof.

Description

BRIEF SUMMARY

The methods and systems described herein provide an approach for sequencing a nucleic acid sample using high throughput methods to detect genetic variants. These methods provide improved methods in the field of diagnosis, assessment and treatment of endometriosis. For example, disclosed herein is the use of nanopore sequencing to detect one or more genetic variants in a nucleic acid sample, wherein the one or more genetic variants are listed in Table 1, Table 2 or Table 3.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned, disclosed or referenced in this specification are herein incorporated by reference in their entirety and to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A-1B is a set of bar charts showing distribution of predictive score using 775 rare variants among 917 endometriosis subjects and 917 controls generated through simulation using the ExAc published frequencies (All rare variants are assumed to be independent).

FIG. 2 is a boxplot of the predictive score across the clinical subtypes of endometriosis. Endoscore is uniform across the severity of endometriosis.

FIG. 3 is a pie chart showing diverse pathways implicated by these 729 genes. No pathway reaches statistical significance, but multiple genes implicated in the Wnt, cadherin, integrin, and inflammation medicated by cytokine signaling pathways.

FIG. 4 is a diagram showing three experimental design strategies. Sequencing nuclear families can help identify Mendelian segregation, whereas relative pairs can help uncover distant relationships with IBD. Unrelated individuals are typically studied to identify common variants with small effects.

FIG. 5 is a diagram showing a nuclear family with an IGF2 mutation on the left and an extended pedigree with a LONP1 mutation to the right.

FIG. 6 is a diagram of mutation patterns cis/trans/haplotypes.

FIG. 7 is a bar chart showing example of results: genes implicated in GWAS (genome-wide association studies) meta-analyses.

FIG. 8A-8C is a set of diagrams showing striking excess of pathogenic mutations (p<10⁻¹⁶).

FIG. 9 is a set of charts showing examples of FN1 and GREB1 in which multiple damaging mutations were found.

FIG. 10 is a diagram showing a computer-based system that may be programmed or otherwise configured to implement methods provided herein.

FIG. 11 is a diagram showing a method and system as disclosed herein.

FIG. 12 shows the whole exome sequencing method used in Example 9.

FIG. 13 shows the sample population of Example 9 of 137 women with surgically confirmed endometriosis and a common ancestor born in 1608.

FIG. 14 shows a common ancestor in GenDB 15-17 generations ago.

FIG. 15 shows a three generation family with 7 women affected with endometriosis is shown in FIG. 15A with a brief clinical description of their endometriosis-related symptoms tabularized in FIG. 15B. in addition, patient 1 has been diagnosed with 14 additional co-morbidities including: Crohn's disease, interstitial cystitis, urinary bladder diverticulum, bronchial asthma, osteoporosis, multinodual goiter, cardiovascular disease, gastroesophageal reflux disease, malignant tumor of urinary bladder, Barrett's esophagus, lupus erythematosus, ankylosing spondyitis, multiple sclerosis, and bilateral cataract.

FIG. 16 shows the chromosomal position and characteristics of the genetic variants surrounding the hemizygous deletions is shown to the left, and the genotypes for each of the seven affected women is shown to the right. Bold boarders indicate the extent of the deletion and the individual that carries the deletions. Thin boarders indicate possible carriers of the deletion.

FIG. 17 shows results of Example 11 including number and percentage of matched probands.

FIG. 18 shows the materials and methods of Example 11.

FIG. 19 shows percentage of affected subjects in both the index pedigree and unrelated pedigrees.

FIG. 20 shows the rate of surgically diagnosed endometriosis.

DETAILED DESCRIPTION

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of the ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the compositions or unit doses herein, some methods and materials are now described. Unless mentioned otherwise, the techniques employed or contemplated herein are standard methodologies. The materials, methods and examples are illustrative only and not limiting.

The details of one or more inventive instances are set forth in the accompanying drawings, the claims, and the description herein. Other features, objects, and advantages of the inventive instances disclosed and contemplated herein can be combined with any other instance unless explicitly excluded.

In some of many aspects, the disclosure provides methods of using genetic markers associated with endometriosis, for example via a computer-implemented program to predict risk of developing endometriosis, and methods of preventing or treating endometriosis or a symptom thereof. The methods disclosed herein can prevent or cancel an invasive procedure, such as a laparoscopy, that would otherwise have been performed on a subject but for the results, for example a (negative) diagnosis/prognosis, from the methods disclosed herein performed on the subject.

In some cases, genetic markers disclosed herein can be used for early diagnosis and prognosis of endometriosis, as well as early clinical intervention to mitigate progression of the disease. The use of these genetic markers can allow selection of subjects for clinical trials involving novel treatment methods. In some instances, genetic markers disclosed herein can be used to predict endometriosis and endometriosis progression, for example in treatment decisions for individuals who are recognized as having endometriosis. In some instances, genetic markers disclosed herein can enable prognosis of endometriosis in much larger populations compared with the populations which can currently be evaluated by using existing risk factors and biomarkers.

In some cases, disclosed herein is a method for endometriosis diagnosis/prognosis that can utilize detection of endometriosis associated biomarkers such as single nucleotide polymorphisms (SNPs), insertion deletion polymorphisms (indels), damaging mutation variants, loss of function variants, synonymous mutation variants, nonsynonymous mutation variants, nonsense mutations, recessive markers, splicing/splice-site variants, frameshift mutations, insertions, deletions, genomic rearrangements, stop-gain, stop-loss, Rare Variants (RVs), some of which are identified in Tables 1-4 (or diagnostically and predicatively functionally comparable biomarkers). In some instances, the method can comprise using a statistical assessment method such as Multi Dimensional Scaling analysis (MDS), logistic regression, machine learning, or Bayesian analysis.

Some of the variants listed in Table 1 can be splicing variants, for example TMED3(NM_007364:exon1:c.168+1G>A), NM_001276480:c.-160+1G>A, KCNK6(NM_004823:exon2:c.323-1G>A), RGPD4(NM_182588:exon19:c.2606-1G>T), NM_001001891:exon18:c.1988+1G>A, NM_001882:exon3:c.176-2->C. The NM number indicates that a particular GenBank cDNA reference sequence was used for reference. The “c” indicates that the nucleotide number which follows is based on coding DNA sequence. The numbers provide the position of the mutation in the DNA. For instance, 168+1G>A means one base after (+1) the 168th coding nucleotide at the end of the exon is mutated from a G to an A. Likewise for NM_182588:exon19:c.2606-1G>T, one base before (−1) the 2606th coding nucleotide. NM_001882:exon3:c.176-2->C involves an insertion of a C.

In some cases, disclosed herein is a treatment method to a subject determined to have or be predisposed to endometriosis. In some instances, the method can comprise administering to the subject a hormone therapy or an assisted reproductive technology therapy. In some instances, the method can comprise administering to the subject a therapy that at least partially compensates for endometriosis, prevents or reduces the severity of endometriosis that the subject would otherwise develop, or prevents endometriosis related complications, cancers, or associated disorders.

In some cases, provided herein is identification of new variants such as SNPs or indels, unique combinations of such variants, and haplotypes of variants that are associated with endometriosis and related pathologies. In some instances, the polymorphisms disclosed herein can be directly useful as targets for the design of diagnostic reagents and the development of therapeutic agents for use in the diagnosis and treatment of endometriosis and related pathologies. Based on the identification of variants associated with endometriosis, the disclosure can provide methods of detecting these variants as well as the design and preparation of detection reagents needed to accomplish this task. Provided herein are novel variants in genetic sequences involved in endometriosis, methods of detecting these variants in a test sample, methods of identifying individuals who have an altered risk of developing endometriosis and for suggesting treatment options for endometriosis based on the presence of a variant(s) disclosed herein or its encoded product and methods of identifying individuals who are more or less likely to respond to a treatment.

In some cases, provided herein are variants such as SNPs and indels associated with endometriosis, nucleic acid molecules containing variants, methods and reagents for the detection of the variants disclosed herein, uses of these variants for the development of detection reagents, and assays or kits that utilize such reagents. In some instances, the variants disclosed herein can be useful for diagnosing, screening for, and evaluating predisposition to endometriosis and progression of endometriosis. In some instances, the variants can be useful in the determining individual subject treatment plans and design of clinical trials of devices for possible use in the treatment of endometriosis. In some instances, the variants and their encoded products can be useful targets for the development of therapeutic agents. In some instances, the variants combined with other non-genetic clinical factors can be useful for diagnosing, screening, evaluating predisposition to endometriosis, assessing risk of progression of endometriosis, determining individual subject treatment plans and design of clinical trials of devices for possible use in the treatment of endometriosis. In some instances, the variants can be useful in the selection of recipients for an oral contraceptive type therapeutic.

Definitions

Unless otherwise indicated, open terms for example “contain,” “containing,” “include,” “including,” and the like mean comprising.

The singular forms “a”, “an”, and “the” are used herein to include plural references unless the context clearly dictates otherwise. Accordingly, unless the contrary is indicated, the numerical parameters set forth in this application are approximations that may vary depending upon the desired properties sought to be obtained by the present invention.

Unless otherwise indicated, some instances herein contemplate numerical ranges. When a numerical range is provided, unless otherwise indicated, the range includes the range endpoints. Unless otherwise indicated, numerical ranges include all values and subranges therein as if explicitly written out. Unless otherwise indicated, any numerical ranges and/or values herein, following or not following the term “about,” can be at 85-115% (i.e., plus or minus 15%) of the numerical ranges and/or values.

As used herein, “endometriosis” can refer to any nonmalignant disorder in which functioning endometrial tissue is present in a location in the body other than the endometrium of the uterus, i.e. outside the uterine cavity or is present within the myometrium of the uterus. For purposes herein it also includes conditions, such as adenomyosis/adenomyoma, that exhibit myometrial tissue in the lesions. Endometriosis can include endometriosis externa, endometrioma, adenomyosis, adenomyomas, adenomyotic nodules of the uterosacral ligaments, endometriotic nodules other than of the uterosacral ligaments, autoimmune endometriosis, mild endometriosis, moderate endometriosis, severe endometriosis, superficial (peritoneal) endometriosis, deep (invasive) endometriosis, ovarian endometriosis, endometriosis-related cancers, and/or “endometriosis-associated conditions”. Unless stated otherwise, the term endometriosis is used herein to describe any of these conditions.

As used herein, “treatment” includes one or more of: reducing the frequency and/or severity of symptoms, elimination of symptoms and/or their underlying cause, and improvement or remediation of damage. For example, treatment of endometriosis includes, for example, relieving the pain experienced by a woman suffering from endometriosis, and/or causing the regression or disappearance of endometriotic lesions.

As used herein, a “therapeutic” can include a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof. In some embodiments, a medical device may comprise a spinal brace. In some embodiments a medical device may comprise an artificial disc device. A medical device may comprise a surgical implant. A pharmaceutical composition may comprise a muscle relaxant, an anti-depressant, a steroid, an opioid, a cannabis-based therapeutic, acetaminophen, a non-steroidal anti-inflammatory, a neuropathic agent, a cannabis, a progestin, a progesterone, or any combination thereof. A neuropathic agent may comprise gabapentin. A non-steroidal anti-inflammatory may comprise naproxen, ibuprofen, a COX-2 inhibitor, or any combination thereof. A pharmaceutical composition may comprises a biologic agent, cellular therapy, regenerative medicine therapy, a tissue engineering approach, a stem cell transplantation or any combination thereof. A medical procedure may comprise an epidural injection (such as a steroid injection), acupuncture, exercise, physical therapy, an ultrasound, a radiofrequency ablation, a surgical therapy, a chiropractic manipulation, an osteopathic manipulation, or any combination thereof. A therapeutic can include a regenerative therapy such as a protein, a stem cell, a cord blood cell, an umbilical cord tissue, a tissue, or any combination thereof. A therapeutic can include cannabis. A therapeutic can include a biosimilar.

“Haplotype” can mean a combination of genotypes on the same chromosome occurring in a linkage disequilibrium block. Haplotypes serve as markers for linkage disequilibrium blocks, and at the same time provide information about the arrangement of genotypes within the blocks. Typing of only certain variants which serve as tags can, therefore, reveal all genotypes for variants located within a block. Thus, the use of haplotypes greatly facilitates identification of candidate genes associated with diseases and drug sensitivity.

“Linkage disequilibrium” or “LD” can mean that a particular combination of alleles (alternative nucleotides) or genetic variants for example at two or more different SNP (or RV) sites are non-randomly co-inherited (i.e., the combination of alleles at the different SNP (or RV) sites occurs more or less frequently in a population than the separate frequencies of occurrence of each allele or the frequency of a random formation of haplotypes from alleles in a given population). The term “LD” can differ from “linkage,” which describes the association of two or more loci on a chromosome with limited recombination between them. LD can also be used to refer to any non-random genetic association between allele(s) at two or more different SNP (or RV) sites. In some instances, when a genetic marker (e.g. SNP or RV) is identified as the genetic marker associated with a disease (in this instance endometriosis), it can be the minor allele (MA) of the particular genetic marker that is associated with the disease. In some instances, if the Odds Ratio (OR) of the MA is greater than 1.0, the MA of the genetic marker (in this instance the endometriosis associated genetic marker) can be correlated with an increased risk of endometriosis in a case subject as compared to a control subject and can be considered a causative marker (C), and if the OR of the MA less than 1.0, the MA of the genetic marker can be correlated with a decreased risk of endometriosis in a case subject as compared to a control subject and can be considered a protective marker (P). “Linkage disequilibrium block” or “LD block” can mean a region of the genome that contains multiple variants located in proximity to each other and that are transmitted as a block.

Biological samples obtained from individuals (e.g., human subjects) may be any sample from which a genetic material (e.g., nucleic acid sample) may be derived. Samples/Genetic materials may be from buccal swabs, saliva, blood, hair, nail, skin, cell, or any other type of tissue sample. In some instances, the genetic material (e.g., nucleic acid sample) comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof. In some instances, the genetic material (e.g., nucleic acid sample) comprises PCR amplified nucleic acids produced from cDNA or mRNA. In some instances, the genetic material (e.g., nucleic acid sample) comprises PCR amplified nucleic acids produced from genomic DNA.

As used herein, the term “cell-free” or “cell free” can refer to the condition of the nucleic acid sequence as it appeared in the body before the sample is obtained from the body. For example, circulating cell-free nucleic acid sequences in a sample may have originated as cell-free nucleic acid sequences circulating in the bloodstream of the human body. In contrast, nucleic acid sequences that are extracted from a solid tissue, such as a biopsy, are generally not considered to be “cell-free.” In some cases, cell-free DNA may comprise fetal DNA, maternal DNA, or a combination thereof. In some cases, cell-free DNA may comprise DNA fragments released into a blood plasma. In some cases, the cell-free DNA may comprise circulating tumor DNA. In some cases, cell-free DNA may comprise circulating DNA indicative of a tissue origin, a disease or a condition. A cell-free nucleic acid sequence may be isolated from a blood sample. A cell-free nucleic acid sequence may be isolated from a plasma sample. A cell-free nucleic acid sequence may comprise a complementary DNA (cDNA). In some cases, one or more cDNAs may form a cDNA library.

Analysis of Rare and Private Mutations in Sequenced Endometriosis Genes

In some cases, the disclosure provides an analysis to evaluate a coding region of a gene as a component of a genetic diagnostic or predictive test for endometriosis. In some instances, the analysis can comprise one or more of the approaches disclosed herein.

In some instances, the analysis can comprise performing DNA variant search on the next generation sequencing output file using a standard software designed for this purpose, for example Life Technologies TMAP algorithm with their default parameter settings, and Life Technologies Torrent Variant Caller software. ANNOVAR can be used to classify coding variants as synonymous, missense, frameshift, splicing, stop-gain, or stop-loss. Variants can be considered “loss-of-function” if the variant causes a stop-loss, stop-gain, splicing, or frame-shift insertion or deletion).

In some instances, the analysis can comprise evaluating prediction of an effect of each variant on protein function in silico using a variety of different software algorithms: Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, MetaLR, or any combination thereof. Missense variants can be deemed “damaging” if they are predicted to be damaging by at least one of the seven algorithms tested.

In some instances, the analysis can comprise searching population databases (e.g., gnomAD) and proprietary endometriosis allele frequency databases for the prevalence of any loss of function or damaging mutations identified by these analyses. The log of the odds ratio can be used to weight the marker when the variant has been previously observed in the reference databases. When a damaging variant or loss of function variant has never been reported in the reference databases, a default odds ratio of 10 can be used to weight the finding.

In some instances, the analysis can comprise incorporating findings into the Risk Score as with the other low-frequency alleles. Risk Score=Summation [log(OR)×Count], where count equals the number of low frequency alleles detected at each endometriosis associated locus. Risk scores can be converted to probability using a nomogram based on confirmed diagnoses.

In some instances, the methods of the disclosure can provide a high sensitivity of detecting gene mutations and diagnosing endometriosis that is greater than 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or more. In some instances, the methods disclosed herein can provide a high specificity of detecting and classifying gene mutations and endometriosis, for example, greater than 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or more. In some instances, a nominal specificity for the method disclosed herein can be greater than or equal to 70%. In some instances, a nominal Negative Predictive Value (NPV) for the method disclosed herein can be greater than or equal to 95%. In some instances, a NPV for the method disclosed herein can be about 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or more. In some instances, a nominal Positive Predictive Value (PPV) for the method disclosed herein can be greater than or equal to 95%. In some instances, a PPV for the method disclosed herein can be about 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or more. In some instances, the accuracy of the methods disclosed herein in diagnosing endometriosis can be greater than 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or more.

Computer Implemented Methods

In some aspects, the disclosure provides methods for analysis of gene sequence data associated software and computer systems. The method, for example being computer implemented, can enable a clinical geneticist or other healthcare technician to sift through vast amounts of gene sequence data, to identify potential disease-causing genomic variants. In some cases, the gene sequence data is from a patient who may be suspected of having a genetic disorder such as endometriosis.

In some cases, provided herein is a method for identifying a genetic disorder such as endometriosis or predicting a risk thereof in an individual, or identifying a genetic variant that is causative of a phenotype in an individual. In some instances, the method can comprise determining gene sequence for a patient suspected of having a genetic disorder, identifying sequence variants, annotating the identified variants based on one or more criteria, and filtering or searching the variants at least partially based on the annotations, to thereby identify potential disease-causing variants.

In some instances, the gene sequence is obtained by use of a sequencing instrument, or alternatively, gene sequence data is obtained from another source, such as for example, a commercial sequencing service provider. Gene sequence can be chromosomal sequence, cDNA sequence, or any nucleotide sequence information that allows for detection of genetic disease. Generally, the amount of sequence information is such that computational tools are required for data analysis. For example, the sequence data may represent at least half of the individual's genomic or cDNA sequence (e.g., of a representative cell population or tissue), or the individuals entire genomic or cDNA sequence. In various embodiments, the sequence data comprises the nucleotide sequence for at least 1 million base pairs, at least 10 million base pairs, or at least 50 million base pairs. In certain embodiments, the DNA sequence is the individual's exome sequence or full exonic sequence component (i.e., the exome; sequence for each of the exons in each of the known genes in the entire genome). In some embodiments, the source of genomic DNA or cDNA may be any suitable source, and may be a sample particularly indicative of a disease or phenotype of interest, including blood cells (e.g, PBMCs, or a T-cell or B-cell population). In certain embodiments, the source of the sample is a tissue or sample that is potentially malignant.

In some instances, whole genome sequence can comprise the entire sequence (including all chromosomes) of an individual's germline genome. In some embodiments, the concatenated length for a whole genome sequence is approximately 3.2 Gbases or 3.2 billion nucleotides.

The term “subject,” as used herein, may be any animal or living organism. Animals can be mammals, such as humans, non-human primates, rodents such as mice and rats, dogs, cats, pigs, sheep, rabbits, and others. A subject may be a dog. A subject may be a human. Animals can be fish, reptiles, or others. Animals can be neonatal, infant, adolescent, or adult animals. Humans can be more than about: 1, 2, 5, 10, 20, 30, 40, 50, 60, 65, 70, 75, or about 80 years of age. The subject may have or be suspected of having a condition or a disease, such as endometriosis or related condition. The subject may be a patient, such as a patient being treated for a condition or a disease, such as a patient suffering from endometriosis. The subject may be predisposed to a risk of developing a condition or a disease such as endometriosis. The subject may be in remission from a condition or a disease, such as a patient recovering from endometriosis. The subject may be healthy. The subject may be a subject in need thereof. The subject may be a female subject or a male subject.

The term “sequencing” as used herein, may comprise high-throughput sequencing, next-gen sequencing, Maxam-Gilbert sequencing, massively parallel signature sequencing, Polony sequencing, 454 pyrosequencing, pH sequencing, Sanger sequencing (chain termination), Illumina sequencing, SOLiD sequencing, Ion Torrent semiconductor sequencing, DNA nanoball sequencing, Heliscope single molecule sequencing, single molecule real time (SMRT) sequencing, nanopore sequencing, shot gun sequencing, RNA sequencing, Enigma sequencing, sequencing-by-hybridization, sequencing-by-ligation, or any combination thereof. The sequencing output data may be subject to quality controls, including filtering for quality (e.g., confidence) of base reads. Exemplary sequencing systems include 454 pyrosequencing (454 Life Sciences), Illumina (Solexa) sequencing, SOLiD (Applied Biosystems), and Ion Torrent Systems' pH sequencing system. In some cases, a nucleic acid of a sample may be sequenced without an associated label or tag. In some cases, a nucleic acid of a sample may be sequenced, the nucleic acid of which may have a label or tag associated with it.

In some instances, the gene sequence may be determined by any suitable method. For example, the gene sequence may be a cDNA sequence determined by clonal amplification (e.g., emulsion PCR) and sequencing. Base calling may be conducted based on any available method, including Sanger sequencing (chain termination), pH sequencing, pyrosequencing, sequencing-by-hybridization, sequencing-by-ligation, etc. The sequencing output data may be subject to quality controls, including filtering for quality (e.g., confidence) of base reads. Exemplary sequencing systems include 454 pyrosequencing (454 Life Sciences), Illumina (Solexa) sequencing, SOLiD (Applied Biosystems), and Ion Torrent Systems' pH sequencing system. In some embodiment, sequencing can be performed by nanopore sequencing. For example, Oxford nanopore sequencing.

Nanopores may be used to sequence, a sample, a small portion (such as one full gene or a portion of one gene), a substantial portion (such as multiple genes or multiple chromosomes), or the entire genomic sequence of an individual. Nanopore sequencing technology may be commercially available or under development from Sequenom (San Diego, Calif.), Illumina (San Diego, Calif.), Oxford Nanopore Technologies LTD (Kidlington, United Kingdom), and Agilent Laboratories (Santa Clara, Calif.). Nanopore sequencing methods and apparatus are have been described in the art and for example are provided in U.S. Pat. No. 5,795,782, herein incorporated by reference in its entirety.

Nanopore sequencing can use electrophoresis to transport a sample through a pore. A nanopore system may contain an electrolytic solution such that when a constant electric field is applied, an electric current can be observed in the system. The magnitude of the electric current density across a nanopore surface may depend on the nanopore's dimensions and the composition of the sample that is occupying the nanopore. During nanopore sequencing, when a sample approaches and or goes through the nanopore, the samples cause characteristic changes in electric current density across nanopore surfaces, these characteristic changes in the electric current enables identification of the sample. Nanopores used herein may be solid-state nanopores, protein nanopores, or hybrid nanopores comprising protein nanopores or organic nanotubes such as carbon or graphene nanotubes, configured in a solid-state membrane, or like framework. In some embodiments, nanopore sequencing can be biological, a solid state nanopore or a hybrid biological/solid state nanopore.

In some instances, a biological nanopore can comprise transmembrane proteins that may be embedded in lipid membranes. In some embodiments, a nanopore described herein may comprise alpha hemolysin. In some embodiments, a nanopore described herein may comprise Mycobacterium smegmatis porin.

Solid state nanopores do not incorporate proteins into their systems. Instead, solid state nanopore technology uses various metal or metal alloy substrates with nanometer sized pores that allow samples to pass through. Solid state nanopores may be fabricated in a variety of materials including but not limited to, silicon nitride (Si₃N₄), silicon dioxide (SiO₂), and the like. In some instances, nanopore sequencing may comprise use of tunneling current, wherein a measurement of electron tunneling through bases as sample (ssDNA) translocates through the nanopore is obtained. In some embodiments, a nanopore system can have solid state pores with single walled carbon nanotubes across the diameter of the pore. In some embodiments, nanoelectrodes may be used on a nanopore system described herein. In some embodiments, fluorescence can be used with nanopores, for example solid state nanopores and fluorescence. For example, In such a system the fluorescence sequencing method converts each base of a sample into a characteristic representation of multiple nucleotides which bind to a fluorescent probe strand-forming dsDNA (were the sample comprises DNA). Where a two color system is used, each base is identified by two separate fluorescence, and will therefore be converted into two specific sequences. Probes may consist of a fluorophore and quencher at the start and end of each sequence, respectively. Each fluorophore may be extinguished by the quencher at the end of the preceding sequence. When the dsDNA is translocating through a solid state nanopore, the probe strand may be stripped off, and the upstream fluorophore will fluoresce.

In some embodiments, a 1-100 nm channel or aperture may be formed through a solid substrate, usually a planar substrate, such as a membrane, through which an analyte, such as single stranded DNA, is induced to translocate. In other embodiments, a 2-50 nm channel or aperture is formed through a substrate; and in still other embodiments, a 2-30 nm, or a 2-20 nm, or a 3-30 nm, or a 3-20 nm, or a 3-10 nm channel or aperture if formed through a substrate.

In some embodiments, nanopores used in connection with the methods and devices of the invention are provided in the form of arrays, such as an array of clusters of nanopores, which may be disposed regularly on a planar surface. In some embodiments, clusters are each in a separate resolution limited area so that optical signals from nanopores of different clusters are distinguishable by the optical detection system employed, but optical signals from nanopores within the same cluster cannot necessarily be assigned to a specific nanopore within such cluster by the optical detection system employed.

In some instances, the gene sequence may be mapped with one or more reference sequences to identify sequence variants. For example, the base reads are mapped against a reference sequence, which in various embodiments is presumed to be a “normal” non-disease sequence. The DNS sequence derived from the Human Genome Project is generally used as a “premier” reference sequence. A number of mapping applications are known, and include TMAP, BWA, GSMAPPER, ELAND, MOSAIK, and MAQ. Various other alignment tools are known, and could also be implemented to map the base reads.

In some cases, based on the sequence alignments, and mapping results, sequence variants can be identified. Types of variants may include insertions, deletions, indels (a colocalized insertion and deletion), damaging mutation variants, loss of function variants, synonymous mutation variants, nonsynonymous mutation variants, nonsense mutations, recessive markers, splicing/splice-site variants, frameshift mutation, insertions, deletions, genomic rearrangements, stop-gain, stop-loss, Rare Variants (RVs), translocations, inversions, and substitutions. While the type of variants analyzed is not limited, the most numerous of the variant types will be single nucleotide substitutions, for which a wealth of data is currently available. In various embodiments, comparison of the test sequence with the reference sequence will produce at least 500 variants, at least 1000 variants, at least 3,000 variants, at least 5,000 variants, at least 10,000 variants, at least 20,000 variants, or at least 50,000 variants, but in some embodiments, will produce at least 1 million variants, at least 2 million variants, at least 3 million variants, at least 4 million variants, or at least 10 million variants. The tools provided herein enable the user to navigate the vast amounts of genetic data to identify potentially disease-causing variants.

In some cases, a wealth of data can be extracted for the identified variants, including one or more of conservation scores, genic/genomic location, zygosity, SNP ID, Polyphen, FATHMM, LRT, Mutation Accessor, and SIFT predictions, splice site predictions, amino acid properties, disease associations, annotations for known variants, variant or allele frequency data, and gene annotations. Data may be calculated and/or extracted from one or more internal or external databases. Since certain categories of annotations (e.g., amino acid properties/PolyPhen and SIFT data) are dependent on a nature of the region of the genome in which they are contained (e.g., whether a variant is contained within a region translated to give rise to an amino acid sequence in a resultant protein), these annotations can be carried out for each known transcript. Exemplary external databases include OMIM (Online Mendelian Inheritance in Man), HGMD (The Human Gene Mutation Databse), PubMed, PolyPhen, SIFT, SpliceSite, reference genome databases, the University of California Santa Cruz (UCSC) genome database, CLINVAR database, the BioBase biological databases, the dbSNP Short Genetic Variations database, the Rat Genome Database (RGD), and/or the like. Various other databases may be employed for extracting data on identified variants. Variant information may be further stored in a central data repository, and the data extracted for future sequence analyses.

In some instances, variants may be tagged by the user with additional descriptive information to aid subsequent analysis. For example, confidence in the existence of the variant can be recorded as confirmed, preliminary, or sequence artifact. Certain sequencing technologies have a tendency to produce certain types of sequence artifacts, and the method herein can allow such suspected artifacts to be recorded. The variants may be further tagged in basic categories of benign, pathogenic, or unknown, or as potentially of interest.

In some instances, queries can be run to identify variants meeting certain criteria, or variant report pages can be browsed by chromosomal position or by gene, the latter allowing researchers to focus on only those variations that exist in a particular set of genes of interest. In some embodiments, the user selects only variants with well-documented and published disease associations (e.g., by filtering based on HGMD or other disease annotation). Alternatively, the user can filter for variants not previously associated with disease, but of a type likely to be deleterious, such as those introducing frameshifts, non-synonymous substitutions (predicted by Polyphen or SIFT), or premature terminations. Further, the user can exclude from analysis those variants believed to be neutral (based on their frequency of occurrence in studies populations), for example, through exclusion of variants in dbSNP. Additional exclusion criteria include mode of inheritance (e.g., heterozygosity), depth of coverage, and quality score.

In certain embodiments, base calling is carried out to extract the sequence of the sequencing reads from an image file produced by an instrument scanner. Following base calling and base quality trimming/filtering, the reads are mapped against a reference sequence (assumed to be normal for the phenotype under analysis) to identify variations (variants) between the two with the assumption that one or more of these differences will be associated with phenotype of the individual whose DNA is under analysis. Subsequently, each variant is annotated with data that can be used to determine the likelihood that that particular variant is associated with the phenotype under analysis. The analysis may be fully or partially automated as described in detail below, and may include use of a central repository for data storage and analysis, and to present the data to analysts and clinical geneticists in a format that makes identification of variants with a high likelihood of being associated with the phenotypic difference more efficient and effective.

In some embodiments, a user can be provided with the ability to run cross sample queries where the variants from multiple samples are interrogated simultaneously. In such embodiments, for example, a user can build a query to return data on only those variants that are exactly shared across a user defined group of samples. This can be useful for family based analyses where the same variant is believed to be associated with disease in each of the affected family members. For another example, the user can also build a query to return only those variants that are present in genes where the gene contains at least one, but not necessarily the same, variant. This can be useful where a group of individuals with disease are not related (the variants associated with the disease are not necessary exactly the same, but result in a common alteration in normal function). For yet another example, the user can specify to ignore genes containing variants in a user defined group of samples. This can be useful to exclude polymorphisms (variants believed or confirmed not to be associated with disease) where the user has access to a user defined group of control individuals who are believed to not have the disease associated variant. For each of these queries a user can additionally filter the variants by specifying any or all of the previously discussed filters on top of the cross sample analyses. This allows a user to identify variants matching these criteria, which are shared between or segregated amongst samples.

For example, a variant analysis system can be implemented locally, or implemented using a host device and a network or cloud computing. For example, the variant analysis system can be software stored in memory of a personal computing device (PC) and implemented by a processor of the PC. In such embodiments, for example, the PC can download the software from a host device and/or install the software using any suitable device such as a compact disc (CD).

The method may employ a computer-readable medium, or non-transitory processor-readable medium. Some embodiments described herein relate to a computer storage product with a non-transitory computer-readable medium (also can be referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The media and computer code (also can be referred to as code) may be those designed and constructed for the specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to: magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as Compact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read Only Memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices that are specially configured to store and execute program code, such as Application-Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read-Only Memory (ROM) and Random-Access Memory (RAM) devices.

Examples of computer code can include, but are not limited to, micro-code or micro-instructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed by a computer using an interpreter. For example, embodiments may be implemented using Python, Java, C++, or other programming languages (e.g., object-oriented programming languages) and development tools. Additional examples of computer code can include, but are not limited to, control signals, encrypted code, and compressed code.

In some cases, variants provided herein may be “provided” in a variety of mediums to facilitate use thereof. As used in this section, “provided” can refer to a manufacture, other than an isolated nucleic acid molecule, that contains variant information of the disclosure. Such a manufacture provides the variant information in a form that allows a skilled artisan to examine the manufacture using means not directly applicable to examining the variants or a subset thereof as they exist in nature or in purified form. The variant information that may be provided in such a form includes any of the variant information provided by the disclosure such as, for example, polymorphic nucleic acid and/or amino acid sequence information, information about observed variant alleles, alternative codons, populations, allele frequencies, variant types, and/or affected proteins, or any other information provided herein.

In some instances, the variants can be recorded on a computer readable medium. As used herein, “computer readable medium” can refer to any medium that can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable media can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the disclosure. One such medium is provided with the present application, namely, the present application contains computer readable medium (CD-R) that has nucleic acid sequences (and encoded protein sequences) containing variants provided/recorded thereon in ASCII text format in a Sequence Listing along with accompanying Tables that contain detailed variant and sequence information.

As used herein, “recorded” can refer to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently known methods for recording information on computer readable medium to generate manufactures comprising the variant information of the disclosure. A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide or amino acid sequence of the disclosure. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide/amino acid sequence information of the disclosure on computer readable medium. For example, the sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, represented in the form of an ASCII file, or stored in a database application, such as OB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data processor structuring formats (e.g., text file or database) in order to obtain computer readable medium having recorded thereon the variant information of the disclosure.

By providing the variants in computer readable form, a skilled artisan can access the variant information for a variety of purposes. Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. Examples of publicly available computer software include BLAST and BLAZE search algorithms.

In some cases, the disclosure can provide systems, particularly computer-based systems, which contain the variant information described herein. Such systems may be designed to store and/or analyze information on, for example, a large number of variant positions, or information on variant genotypes from a large number of individuals. The variant information of the disclosure represents a valuable information source. The variant information of the disclosure stored/analyzed in a computer-based system may be used for such computer-intensive applications as determining or analyzing variant allele frequencies in a population, mapping endometriosis genes, genotype-phenotype association studies, grouping variants into haplotypes, correlating variant haplotypes with response to particular treatments or for various other bioinformatic, pharmacogenomic or drug development.

As used herein, “a computer-based system” can refer to the hardware means, software means, and data storage means used to analyze the variant information of the disclosure. The minimum hardware means of the computer-based systems of the disclosure typically comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based systems are suitable for use in the disclosure. Such a system can be changed into a system of the disclosure by utilizing the variant information provided on the CD-R, or a subset thereof, without any experimentation.

As stated above, the computer-based systems can comprise a data storage means having stored therein variants of the disclosure and the necessary hardware means and software means for supporting and implementing a search means. As used herein, “data storage means” can refer to memory which can store variant information of the disclosure, or a memory access means which can access manufactures having recorded thereon the variant information of the disclosure.

As used herein, “search means” can refer to one or more programs or algorithms that are implemented on the computer-based system to identify or analyze variants in a target sequence based on the variant information stored within the data storage means. Search means can be used to determine which nucleotide is present at a particular variant position in the target sequence. As used herein, a “target sequence” can be any DNA sequence containing the variant position(s) to be searched or queried.

A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the disclosure. An exemplary format for an output means is a display that depicts the presence or absence of specified nucleotides (alleles) at particular variant positions of interest. Such presentation can provide a rapid, binary scoring system for many variants simultaneously.

In some cases, the disclosure provides computer-based systems that are programmed to implement methods of the disclosure. FIG. 10 shows a computer system 101 that can be programmed or configured for endometriosis diagnosis. The computer system 101 can regulate various aspects of detection of genetic variants associated with endometriosis of the disclosure. The computer system 101 can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

The computer system 101 includes a central processing unit (CPU, also “processor” and “computer processor” herein) 105, which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system 101 also includes memory or memory location 110 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 115 (e.g., hard disk), communication interface 120 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 125, such as cache, other memory, data storage and/or electronic display adapters. The memory 110, storage unit 115, interface 120 and peripheral devices 125 are in communication with the CPU 105 through a communication bus (solid lines), such as a motherboard. The storage unit 115 can be a data storage unit (or data repository) for storing data. The computer system 101 can be operatively coupled to a computer network (“network”) 130 with the aid of the communication interface 120. The network 130 can be the Internet, an internet and/or extranet, or an intranet and/or extranet that is in communication with the Internet. The network 130 in some cases is a telecommunication and/or data network. The network 130 can include one or more computer servers, which can enable distributed computing, such as cloud computing. The network 130, in some cases with the aid of the computer system 101, can implement a peer-to-peer network, which may enable devices coupled to the computer system 101 to behave as a client or a server.

The CPU 105 can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 110. The instructions can be directed to the CPU 105, which can subsequently program or otherwise configure the CPU 105 to implement methods of the disclosure. Examples of operations performed by the CPU 105 can include fetch, decode, execute, and writeback.

The CPU 105 can be part of a circuit, such as an integrated circuit. One or more other components of the system 101 can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

The storage unit 115 can store files, such as drivers, libraries and saved programs. The storage unit 115 can store user data, e.g., user preferences and user programs. The computer system 101 in some cases can include one or more additional data storage units that are external to the computer system 101, such as located on a remote server that is in communication with the computer system 101 through an intranet or the Internet.

The computer system 101 can communicate with one or more remote computer systems through the network 130. For instance, the computer system 101 can communicate with a remote computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC's (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system 101 via the network 130.

Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system 101, such as, for example, on the memory 110 or electronic storage unit 115. The machine executable or machine readable code can be provided in the form of software. During use, the code can be executed by the processor 105. In some cases, the code can be retrieved from the storage unit 115 and stored on the memory 110 for ready access by the processor 105. In some situations, the electronic storage unit 115 can be precluded, and machine-executable instructions are stored on memory 110.

The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code, or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a pre-compiled or as-compiled fashion.

Aspects of the systems and methods provided herein, such as the computer system 101, can be embodied in programming. Various aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code and/or associated data that is carried on or embodied in a type of machine readable medium. Machine-executable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk. “Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

Hence, a machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read programming code and/or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

The computer system 101 can include or be in communication with an electronic display 135 that comprises a user interface (UI) 140 for providing, for example a monitor. Examples of UI's include, without limitation, a graphical user interface (GUI) and web-based user interface.

Methods and systems of the disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit 105. The algorithm can, for example, Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, MetaLR, or any combination thereof.

In some cases, as shown in FIG. 11, a sample 202 containing a genetic material may be obtained from a subject 201, such as a human subject. A sample 202 may be subjected to one or more methods as described herein, such as performing an assay. In some cases, an assay may comprise sequencing (such as nanopore sequencing), genotyping, hybridization, amplification, labeling, or any combination thereof. One or more results from a method may be input into a processor 204. One or more input parameters such as a sample identification, subject identification, sample type, a reference, or other information may be input into a processor 204. One or more metrics from an assay may be input into a processor 204 such that the processor may produce a result, such as a diagnosis of endometriosis or a recommendation for a treatment. A processor may send a result, an input parameter, a metric, a reference, or any combination thereof to a display 205, such as a visual display or graphical user interface. A processor 204 may (i) send a result, an input parameter, a metric, or any combination thereof to a server 207, (ii) receive a result, an input parameter, a metric, or any combination thereof from a server 207, (iii) or a combination thereof.

Methods of Detection of Variants

In some aspects, the disclosure provides methods to detect variants, e.g, detecting a genetic variant in a panel comprising two or more genetic variants defining a minor allele disclosed herein (e.g., in Table 1). In some instances, the detecting comprises, DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof. In some instances, the panel comprises at least: 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 75, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or more genetic variants defining minor alleles disclosed herein (e.g., in Table 1). In some instances, the genetic variant to detect or detected has an odds ratio (OR) of at least: 0.1, 1, 1.5, 2, 5, 10, 20, 50, 100, 127, 130, 140, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, or more. In some embodiments, the OR is at least 127. In some instances, the panel to detect further comprises one or more protein damaging or loss of function variants in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof. In some instances, the panel further comprises one or more additional variants defining a minor allele listed in Table 4.

In some cases, variants of the disclosure may include single nucleotide polymorphisms (SNPs), insertion deletion polymorphisms (indels), damaging mutation variants, loss of function variants, synonymous mutation variants, nonsynonymous mutation variants, nonsense mutations, recessive markers, splicing/splice-site variants, frameshift mutation, insertions, deletions, genomic rearrangements, stop-gain, stop-loss, Rare Variants (RVs), translocations, inversions, and substitutions.

Variants for example SNPs are usually preceded and followed by highly conserved sequences that vary in less than 1/100 or 1/1000 members of the population. An individual may be homozygous or heterozygous for an allele at each SNP position. A SNP may, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP is an amino acid “coding” sequence. A SNP may arise from a substitution of one nucleotide for another at the polymorphic site. Substitutions can be transitions or transversions. A transition is the replacement of one purine nucleotide by another purine nucleotide, or one pyrimidine by another pyrimidine. A transversion is the replacement of a purine by a pyrimidine, or vice versa.

A synonymous codon change, or silent mutation is one that does not result in a change of amino acid due to the degeneracy of the genetic code. A substitution that changes a codon coding for one amino acid to a codon coding for a different amino acid (i.e., a non-synonymous codon change) is referred to as a missense mutation. A nonsense mutation results in a type of non-synonymous codon change in which a stop codon is formed, thereby leading to premature termination of a polypeptide chain and a truncated protein. A read-through mutation is another type of non-synonymous codon change that causes the destruction of a stop codon, thereby resulting in an extended polypeptide product. An indel that occur in a coding DNA segment gives rise to a frameshift mutation.

Causative variants are those that produce alterations in gene expression or in the structure and/or function of a gene product, and therefore are predictive of a possible clinical phenotype. One such class includes SNPs falling within regions of genes encoding a polypeptide product, i.e. cSNPs. These SNPs may result in an alteration of the amino acid sequence of the polypeptide product (i.e., non-synonymous codon changes) and give rise to the expression of a defective or other variant protein. Furthermore, in the case of nonsense mutations, a SNP may lead to premature termination of a polypeptide product. Such variant products can result in a pathological condition, e.g., genetic endometriosis.

An association study of a variant and a specific disorder involves determining the presence or frequency of the variant allele in biological samples from individuals with the disorder of interest, such as endometriosis, and comparing the information to that of controls (i.e., individuals who do not have the disorder; controls may be also referred to as “healthy” or “normal” individuals) who are for example of similar age and race. The appropriate selection of patients and controls is important to the success of variant association studies. Therefore, a pool of individuals with well-characterized phenotypes is extremely desirable.

A variant may be screened in tissue samples or any biological sample obtained from an affected individual, and compared to control samples, and selected for its increased (or decreased) occurrence in a specific pathological condition, such as pathologies related to endometriosis. Once a statistically significant association is established between one or more variant(s) and a pathological condition (or other phenotype) of interest, then the region around the variant can optionally be thoroughly screened to identify the causative genetic locus/sequence(s) (e.g., causative variant/mutation, gene, regulatory region, etc.) that influences the pathological condition or phenotype. Association studies may be conducted within the general population and are not limited to studies performed on related individuals in affected families (linkage studies). For diagnostic and prognostic purposes, if a particular variant site is found to be useful for diagnosing a disease, such as endometriosis, other variant sites which are in LD with this variant site would also be expected to be useful for diagnosing the condition. Linkage disequilibrium is described in the human genome as blocks of variants along a chromosome segment that do not segregate independently (i.e., that are non-randomly co-inherited). The starting (5′ end) and ending (3′ end) of these blocks can vary depending on the criteria used for linkage disequilibrium in a given database, such as the value of D′ or r² used to determine linkage disequilibrium.

In some instances, variants can be identified in a study using a whole-genome case-control approach to identify single nucleotide polymorphisms that were closely associated with the development of endometriosis, as well as variants found to be in linkage disequilibrium with (i.e., within the same linkage disequilibrium block as) the endometriosis-associated variants, which can provide haplotypes (i.e., groups of variants that are co-inherited) to be readily inferred. Thus, the disclosure provides individual variants associated with endometriosis, as well as combinations of variants and haplotypes in genetic regions associated with endometriosis, methods of detecting these polymorphisms in a test sample, methods of determining the risk of an individual of having or developing endometriosis and for clinical sub-classification of endometriosis.

In some cases, the disclosure provides variants associated with endometriosis, as well as variants that were previously known in the art, but were not previously known to be associated with endometriosis. Accordingly, the disclosure provides novel compositions and methods based on the variants disclosed herein, and also provides novel methods of using the known but previously unassociated variants in methods relating to endometriosis (e.g., for diagnosing endometriosis. etc.).

In some instances, particular variant alleles of the disclosure can be associated with either an increased risk of having or developing endometriosis, or a decreased risk of having or developing endometriosis. Variant alleles that are associated with a decreased risk may be referred to as “protective” alleles, and variant alleles that are associated with an increased risk may be referred to as “susceptibility” alleles, “risk factors”, or “high-risk” alleles. Thus, whereas certain variants can be assayed to determine whether an individual possesses a variant allele that is indicative of an increased risk of having or developing endometriosis (i.e., a susceptibility allele), other variants can be assayed to determine whether an individual possesses a variant allele that is indicative of a decreased risk of having or developing endometriosis (i.e., a protective allele). Similarly, particular variant alleles of the disclosure can be associated with either an increased or decreased likelihood of responding to a particular treatment. The term “altered” may be used herein to encompass either of these two possibilities (e.g., an increased or a decreased risk/likelihood).

In some instances, nucleic acid molecules may be double-stranded molecules and that reference to a particular site on one strand refers, as well, to the corresponding site on a complementary strand. In defining a variant position, variant allele, or nucleotide sequence, reference to an adenine, a thymine (uridine), a cytosine, or a guanine at a particular site on one strand of a nucleic acid molecule also defines the complementary thymine (uridine), adenine, guanine, or cytosine (respectively) at the corresponding site on a complementary strand of the nucleic acid molecule. Thus, reference may be made to either strand in order to refer to a particular variant position, variant allele, or nucleotide sequence. Probes and primers may be designed to hybridize to either strand and variant genotyping methods disclosed herein may generally target either strand. Throughout the specification, in identifying a variant position, reference is generally made to the forward or “sense” strand, solely for the purpose of convenience. Since endogenous nucleic acid sequences exist in the form of a double helix (a duplex comprising two complementary nucleic acid strands), it is understood that the variants disclosed herein will have counterpart nucleic acid sequences and variants associated with the complementary “reverse” or “antisense” nucleic acid strand. Such complementary nucleic acid sequences, and the complementary variants present in those sequences, are also included within the scope of the disclosure.

Disclosed herein are methods for detecting genetic variants in a nucleic acid sample. The method can comprise sequencing a nucleic acid sample obtained from a subject having endometriosis or suspected of having endometriosis using a high throughput method. The high throughput method can comprise nanopore sequencing. The method can comprise detecting one or more genetic variants in a nucleic acid sample, wherein the one or more genetic variants are listed in Table 1, Table 2 or Table 3. The nucleic acid sample can comprise RNA. The RNA can comprise mRNA. The nucleic acid sample can comprise DNA. The DNA can comprise cDNA, genomic DNA, sheared DNA, cell free DNA, fragmented DNA, or PCR amplified products produced therefrom, or any combination thereof. The one or more genetic variants can comprise a genetic variant defining a minor allele. The one or more genetic variants can comprise at least about: 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 500, or more genetic variants defining minor alleles. The detection of the one or more genetic variants can have an odds ratio (OR) for endometriosis of at least about: 1.5, 2, 5, 10, 20, 50, 100, or more. The one or more genetic variants can comprise a synonymous mutation, a non-synonymous mutation, a stop-gain mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. The one or more genetic variants can comprise a protein damaging mutation. The one or more genetic variants can comprise a protein damaging or loss of function variant in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof. The one or more genetic variants can be comprised in GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR or a combination thereof. The method can comprise detecting one or more additional variants defining a minor allele listed in Table 4. The one or more genetic variants can be identified based on a predictive computer algorithm. The one or more genetic variants can be identified based on reference to a database. The method can further comprise identifying a subject as having endometriosis or being at risk of developing endometriosis. The method can comprise identifying a subject as having endometriosis or being at risk of developing endometriosis with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. The method can comprise identifying a subject as having endometriosis or being at risk of developing endometriosis with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. The method can comprise identifying a subject as having endometriosis or being at risk of developing endometriosis with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. The method can comprise identifying a subject as having endometriosis. The subject can be asymptomatic for endometriosis. In some cases, the subject can have endometriosis and be asymptomatic. The subject can be symptomatic for endometriosis. The subject can be identified as being at risk of developing endometriosis. The method can further comprise administering a therapeutic to a subject. The therapeutic can comprise hormonal therapy, an advanced reproductive technology therapy, a pain managing medication, or any combination thereof. The therapeutic can comprise hormonal contraceptives, gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn-RH) antagonists, progestin, danazol, or any combination thereof. The therapeutic can comprise a pain medication. The pain medication can comprise a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof. In some cases, the one or more genetic variants are listed in Table 1. In some cases, the one or more genetic variants are listed in Table 2. In some cases, the one or more genetic variants are listed in Table 3. The method can further comprise identifying a subject as having endometriosis-associated infertility or being at risk of developing endometriosis-associated infertility. The method can further comprise administering assisted reproductive technology therapy to a subject. The assisted reproductive technology therapy can comprise in vitro fertilization, gamete intrafallopian transfer, or any combination thereof. The method can further comprise administering, intrauterine insemination or ovulation induction. A subject described herein can be a mammal. The mammal can be a human. Nanopore sequencing can be performed with a biological nanopore, a solid state nanopore, or a hybrid nanopore. Methods disclosed herein can detect 1, 5, 10, 15, 20, 30, 50, 60, 100, 80, 90, 100, 200 or more variants disclosed herein. Genetic variants detected herein can indicate endometriosis or a risk of developing endometriosis. In some embodiments, one or more genetic variant listed in Table 1 are the only genetic variants detected. In some embodiments, one or more genetic variants listed in Table 2 are the only genetic variant detected. In some embodiments, one or more genetic variants listed in Table 3 are the only genetic variant detected. In some embodiments, one or more genetic variant listed in Table 4 are the only genetic variant detected. In other embodiments, one or more genetic variants are detected from two or more of Table 1, Table 2, Table 3 and Table 4.

Genotyping Methods

In some cases, the process of determining which specific nucleotide (i.e., allele) is present at each of one or more variant positions, such as a variant position in a nucleic acid molecule characterized by a variant, is referred to as variant genotyping. The disclosure provides methods of variant genotyping, such as for use in screening for endometriosis or related pathologies, or determining predisposition thereto, or determining responsiveness to a form of treatment, or in genome mapping or variant association analysis, etc.

Nucleic acid samples can be genotyped to determine which allele(s) is/are present at any given genetic region (e.g., variant position) of interest by methods well known in the art. The neighboring sequence can be used to design variant detection reagents such as oligonucleotide probes, which may optionally be implemented in a kit format. Common variant genotyping methods include, but are not limited to, TaqMan assays, molecular beacon assays, nucleic acid arrays, allele-specific primer extension, allele-specific PCR, arrayed primer extension, homogeneous primer extension assays, primer extension with detection by mass spectrometry, mass spectrometry with or with monoisotopic dNTPs (pyrosequencing, multiplex primer extension sorted on genetic arrays, ligation with rolling circle amplification, homogeneous ligation, OLA, multiplex ligation reaction sorted on genetic arrays, restriction-fragment length polymorphism, single base extension-tag assays, and the Invader assay. Such methods may be used in combination with detection mechanisms such as, for example, luminescence or chemiluminescence detection, fluorescence detection, time-resolved fluorescence detection, fluorescence resonance energy transfer, fluorescence polarization, mass spectrometry, electrospray mass spectrometry, and electrical detection.

Various methods for detecting polymorphisms can include, but are not limited to, methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA duplexes, comparison of the electrophoretic mobility of variant and wild type nucleic acid molecules, and assaying the movement of polymorphic or wild-type fragments in polyacrylamide gels containing a gradient of denaturant using denaturing gradient gel electrophoresis (DGGE). Sequence variations at specific locations can also be assessed by nuclease protection assays such as RNase and SI protection or chemical cleavage methods.

In some instances, a variant genotyping can be performed using the TaqMan assay, which is also known as the 5′ nuclease assay. The TaqMan assay detects the accumulation of a specific amplified product during PCR. The TaqMan assay utilizes an oligonucleotide probe labeled with a fluorescent reporter dye and a quencher dye. The reporter dye is excited by irradiation at an appropriate wavelength, it transfers energy to the quencher dye in the same probe via a process called fluorescence resonance energy transfer (FRET). When attached to the probe, the excited reporter dye does not emit a signal. The proximity of the quencher dye to the reporter dye in the intact probe maintains a reduced fluorescence for the reporter. The reporter dye and quencher dye may be at the 5′ most and the 3′ most ends, respectively, or vice versa. Alternatively, the reporter dye may be at the 5′ or 3′ most end while the quencher dye is attached to an internal nucleotide, or vice versa. In yet another embodiment, both the reporter and the quencher may be attached to internal nucleotides at a distance from each other such that fluorescence of the reporter is reduced. During PCR, the 5′ nuclease activity of DNA polymerase cleaves the probe, thereby separating the reporter dye and the quencher dye and resulting in increased fluorescence of the reporter. Accumulation of PCR product is detected directly by monitoring the increase in fluorescence of the reporter dye. The DNA polymerase cleaves the probe between the reporter dye and the quencher dye only if the probe hybridizes to the target variant-containing template which is amplified during PCR, and the probe is designed to hybridize to the target variant site only if a particular variant allele is present. TaqMan primer and probe sequences can readily be determined using the variant and associated nucleic acid sequence information provided herein. A number of computer programs, such as Primer Express (Applied Biosystems, Foster City, Calif.), can be used to rapidly obtain optimal primer/probe sets. It will be apparent to one of skill in the art that such primers and probes for detecting the variants of the disclosure are useful in diagnostic assays for endometriosis and related pathologies, and can be readily incorporated into a kit format. The disclosure also includes modifications of the Taqman assay well known in the art such as the use of Molecular Beacon probes and other variant formats.

In some instances, a method for genotyping the variants can be the use of two oligonucleotide probes in an OLA. In this method, one probe hybridizes to a segment of a target nucleic acid with its 3′ most end aligned with the variant site. A second probe hybridizes to an adjacent segment of the target nucleic acid molecule directly 3′ to the first probe. The two juxtaposed probes hybridize to the target nucleic acid molecule, and are ligated in the presence of a linking agent such as a ligase if there is perfect complementarity between the 3′ most nucleotide of the first probe with the variant site. If there is a mismatch, ligation would not occur. After the reaction, the ligated probes are separated from the target nucleic acid molecule, and detected as indicators of the presence of a variant.

In some instances, a method for variant genotyping is based on mass spectrometry. Mass spectrometry takes advantage of the unique mass of each of the four nucleotides of DNA. variants can be unambiguously genotyped by mass spectrometry by measuring the differences in the mass of nucleic acids having alternative variant alleles. MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time of Flight) mass spectrometry technology is exemplary for extremely precise determinations of molecular mass, such as variants. Numerous approaches to variant analysis have been developed based on mass spectrometry. Exemplary mass spectrometry-based methods of variant genotyping include primer extension assays, which can also be utilized in combination with other approaches, such as traditional gel-based formats and microarrays.

In some instances, a method for genotyping the variants of the disclosure is the use of electrospray mass spectrometry for direct analysis of an amplified nucleic acid. In this method, in one aspect, an amplified nucleic acid product may be isotopically enriched in an isotope of oxygen (O), carbon (C), nitrogen (N) or any combination of those elements. In an exemplary embodiment the amplified nucleic acid is isotopically enriched to a level of greater than 99.9% in the elements of O¹⁶, C¹² and N¹⁴ The amplified isotopically enriched product can then be analyzed by electrospray mass spectrometry to determine the nucleic acid composition and the corresponding variant genotyping. Isotopically enriched amplified products result in a corresponding increase in sensitivity and accuracy in the mass spectrum. In another aspect of this method an amplified nucleic acid that is not isotopically enriched can also have composition and variant genotype determined by electrospray mass spectrometry.

In some instances, variants can be scored by direct DNA sequencing. The nucleic acid sequences of the disclosure enable one of ordinary skill in the art to readily design sequencing primers for such automated sequencing procedures. Commercial instrumentation, such as the Applied Biosystems 377, 3100, 3700, 3730, and 3730.times.1 DNA Analyzers (Foster City, Calif.), is commonly used in the art for automated sequencing.

Variant genotyping can include the steps of, for example, collecting a biological sample from a human subject (e.g., sample of tissues, cells, fluids, secretions, etc.), isolating nucleic acids (e.g., genomic DNA, mRNA or both) from the cells of the sample, contacting the nucleic acids with one or more primers which specifically hybridize to a region of the isolated nucleic acid containing a target variant under conditions such that hybridization and amplification of the target nucleic acid region occurs, and determining the nucleotide present at the variant position of interest, or, in some assays, detecting the presence or absence of an amplification product (assays can be designed so that hybridization and/or amplification will only occur if a particular variant allele is present or absent). In some assays, the size of the amplification product is detected and compared to the length of a control sample; for example, deletions and insertions can be detected by a change in size of the amplified product compared to a normal genotype.

In some instances, a variant genotyping can be used in applications that include, but are not limited to, variant-endometriosis association analysis, endometriosis predisposition screening, endometriosis diagnosis, endometriosis prognosis, endometriosis progression monitoring, determining therapeutic strategies based on an individual's genotype, and stratifying a patient population for clinical trials for a treatment such as minimally invasive device for the treatment of endometriosis.

Analysis of Genetic Association Between Variants and Phenotypic Traits

In some cases, genotyping for endometriosis diagnosis, endometriosis predisposition screening, endometriosis prognosis and endometriosis treatment and other uses described herein, can rely on initially establishing a genetic association between one or more specific variants and the particular phenotypic traits of interest.

In some instances, in a genetic association study, the cause of interest to be tested is a certain allele or a variant or a combination of alleles or a haplotype from several variants. Thus, tissue specimens (e.g., saliva) from the sampled individuals may be collected and genomic DNA genotyped for the variant(s) of interest. In addition to the phenotypic trait of interest, other information such as demographic (e.g., age, gender, ethnicity, etc.), clinical, and environmental information that may influence the outcome of the trait can be collected to further characterize and define the sample set. Specifically, in an endometriosis genetic association study, clinical information such as body mass index, age and diet may be collected. In many cases, these factors are known to be associated with diseases and/or variant allele frequencies. There are likely gene-environment and/or gene-gene interactions as well. Analysis methods to address gene-environment and gene-gene interactions (for example, the effects of the presence of both susceptibility alleles at two different genes can be greater than the effects of the individual alleles at two genes combined) are discussed below.

In some instances, after all the relevant phenotypic and genotypic information has been obtained, statistical analyses are carried out to determine if there is any significant correlation between the presence of an allele or a genotype with the phenotypic characteristics of an individual. For example, data inspection and cleaning are first performed before carrying out statistical tests for genetic association. Epidemiological and clinical data of the samples can be summarized by descriptive statistics with tables and graphs. Data validation is for example performed to check for data completion, inconsistent entries, and outliers. Chi-squared tests may then be used to check for significant differences between cases and controls for discrete and continuous variables, respectively. To ensure genotyping quality, Hardy-Weinberg disequilibrium tests can be performed on cases and controls separately. Significant deviation from Hardy-Weinberg equilibrium (HWE) in both cases and controls for individual markers can be indicative of genotyping errors. If HWE is violated in a majority of markers, it is indicative of population substructure that should be further investigated. Moreover, Hardy-Weinberg disequilibrium in cases only can indicate genetic association of the markers with the disease of interest.

In some instances, to test whether an allele of a single variant is associated with the case or control status of a phenotypic trait, one skilled in the art can compare allele frequencies in cases and controls. Standard chi-squared tests and Fisher exact tests can be carried out on a 2×2 table (2 variant alleles×2 outcomes in the categorical trait of interest). To test whether genotypes of a variant are associated, chi-squared tests can be carried out on a 3×2 table (3 genotypes×2 outcomes). Score tests are also carried out for genotypic association to contrast the three genotypic frequencies (major homozygotes, heterozygotes and minor homozygotes) in cases and controls, and to look for trends using 3 different modes of inheritance, namely dominant (with contrast coefficients 2, −1, −1), additive (with contrast coefficients 1, 0, −1) and recessive (with contrast coefficients 1, 1, −2). Odds ratios for minor versus major alleles, and odds ratios for heterozygote and homozygote variants versus the wild type genotypes are calculated with the desired confidence limits, usually 95%. In the present study a software algorithm, PLINK, has been applied to automate the calculation of Hardy-Weinberg equilibrium, chi-square, p-values and odds-ratios for very large numbers of variants and Case-Control individuals simultaneously.

In some instances, in order to control for confounding effects and to test for interactions a stepwise multiple logistic regression analysis using statistical packages such as SAS or R may be performed. Logistic regression is a model-building technique in which the best fitting and most parsimonious model is built to describe the relation between the dichotomous outcome (for instance, getting a certain endometriosis or not) and a set of independent variables (for instance, genotypes of different associated genes, and the associated demographic and environmental factors). The most common model is one in which the logit transformation of the odds ratios is expressed as a linear combination of the variables (main effects) and their cross-product terms (interactions). To test whether a certain variable or interaction is significantly associated with the outcome, coefficients in the model are first estimated and then tested for statistical significance of their departure from zero.

In some instances, in addition to performing association tests one marker at a time, haplotype association analysis may also be performed to study a number of markers that are closely linked together. Haplotype association tests can have better power than genotypic or allelic association tests when the tested markers are not the disease-causing mutations themselves but are in linkage disequilibrium with such mutations. The test will even be more powerful if the endometriosis is indeed caused by a combination of alleles on a haplotype. In order to perform haplotype association effectively, marker-marker linkage disequilibrium measures, both D′ and r², are typically calculated for the markers within a gene to elucidate the haplotype structure. Variants within a gene can be organized in block pattern, and a high degree of linkage disequilibrium exists within blocks and very little linkage disequilibrium exists between blocks. Haplotype association with the endometriosis status can be performed using such blocks once they have been elucidated.

Haplotype association tests can be carried out in a similar fashion as the allelic and genotypic association tests. Each haplotype in a gene is analogous to an allele in a multi-allelic marker. One skilled in the art can either compare the haplotype frequencies in cases and controls or test genetic association with different pairs of haplotypes. Score tests can be done on haplotypes using the program “haplo.score”. In that method, haplotypes are first inferred by EM algorithm and score tests are carried out with a generalized linear model (GLM) framework that allows the adjustment of other factors.

In some instances, an important decision in the performance of genetic association tests is the determination of the significance level at which significant association can be declared when the p-value of the tests reaches that level. In an exploratory analysis where positive hits will be followed up in subsequent confirmatory testing, an unadjusted p-value<0.1 (a significance level on the lenient side) may be used for generating hypotheses for significant association of a variant with certain phenotypic characteristics of a endometriosis. It is exemplary that a p-value<0.05 (a significance level traditionally used in the art) is achieved in order for a variant to be considered to have an association with a endometriosis. It is more exemplary that a p-value<0.01 (a significance level on the stringent side) is achieved for an association to be declared. Permutation tests to control for the false discovery rates, FDR, can further be employed. Such methods to control for multiplicity would be exemplary when the tests are dependent and controlling for false discovery rates is sufficient as opposed to controlling for the experiment-wise error rates.

In some instances, since both genotyping and endometriosis status classification can involve errors, sensitivity analyses may be performed to see how odds ratios and p-values would change upon various estimates on genotyping and endometriosis classification error rates.

Once individual risk factors, genetic or non-genetic, have been found for the predisposition to endometriosis, the next step can be to set up a classification/prediction scheme to predict the category (for instance, endometriosis or no endometriosis) that an individual will be in depending on his genotypes of associated variants and other non-genetic risk factors. Logistic regression for discrete trait and linear regression for continuous trait are standard techniques for such tasks. Moreover, other techniques can also be used for setting up classification. Such techniques include, but are not limited to, MART, CART, neural network, and discriminant analyses that are suitable for use in comparing the performance of different methods.

Endometriosis Diagnosis and Predisposition Screening

In some cases, information on association/correlation between genotypes and endometriosis-related phenotypes can be exploited in several ways. For example, in the case of a highly statistically significant association between one or more variants with predisposition to a disease for which treatment is available, detection of such a genotype pattern in an individual may justify particular treatment, or at least the institution of regular monitoring of the individual. In the case of a weaker but still statistically significant association between a variant and a human disease, immediate therapeutic intervention or monitoring may not be justified after detecting the susceptibility allele or variant.

The variants disclosed herein may contribute to endometriosis in an individual in different ways. Some polymorphisms occur within a protein coding sequence and contribute to endometriosis phenotype by affecting protein structure. Other polymorphisms occur in noncoding regions but may exert phenotypic effects indirectly via influence on, for example, replication, transcription, and/or translation. A single variant may affect more than one phenotypic trait. Likewise, a single phenotypic trait may be affected by multiple variants in different genes.

The variants disclosed herein may contribute to endometriosis in an individual in different ways. Some polymorphisms occur within a protein coding sequence and contribute to endometriosis phenotype by affecting protein structure. Other polymorphisms occur in noncoding regions but may exert phenotypic effects indirectly via influence on, for example, replication, transcription, and/or translation. A single variant may affect more than one phenotypic trait. Likewise, a single phenotypic trait may be affected by multiple variants in different genes.

Haplotypes can be particularly useful in that, for example, fewer variants can be genotyped to determine if a particular genomic region harbors a locus that influences a particular phenotype, such as in linkage disequilibrium-based variant association analysis.

Linkage disequilibrium (LD) can refer to the co-inheritance of alleles (e.g., alternative nucleotides) at two or more different variant sites at frequencies greater than would be expected from the separate frequencies of occurrence of each allele in a given population. The expected frequency of co-occurrence of two alleles that are inherited independently is the frequency of the first allele multiplied by the frequency of the second allele. Alleles that co-occur at expected frequencies are said to be in “linkage equilibrium”. In contrast, LD can refer to any non-random genetic association between allele(s) at two or more different variant sites, which is generally due to the physical proximity of the two loci along a chromosome. LD can occur when two or more variants sites are in close physical proximity to each other on a given chromosome and therefore alleles at these variant sites will tend to remain unseparated for multiple generations with the consequence that a particular nucleotide (allele) at one variant site will show a non-random association with a particular nucleotide (allele) at a different variant site located nearby. Hence, genotyping one of the variant sites will give almost the same information as genotyping the other variant site that is in LD.

For diagnostic purposes, if a particular variant site is found to be useful for diagnosing endometriosis, then the skilled artisan would recognize that other variant sites which are in LD with this variant site would also be useful for diagnosing the condition. Various degrees of LD can be encountered between two or more variants with the result being that some variants are more closely associated (i.e., in stronger LD) than others. Furthermore, the physical distance over which LD extends along a chromosome differs between different regions of the genome, and therefore the degree of physical separation between two or more variant sites necessary for LD to occur can differ between different regions of the genome.

For diagnostic applications, polymorphisms (e.g., variants and/or haplotypes) that are not the actual disease-causing (causative) polymorphisms, but are in LD with such causative polymorphisms, are also useful. In such instances, the genotype of the polymorphism(s) that is/are in LD with the causative polymorphism is predictive of the genotype of the causative polymorphism and, consequently, predictive of the phenotype (e.g., endometriosis) that is influenced by the causative variant(s). Thus, polymorphic markers that are in LD with causative polymorphisms are useful as diagnostic markers, and are particularly useful when the actual causative polymorphism(s) is/are unknown.

The contribution or association of particular variants and/or variant haplotypes with endometriosis phenotypes, such as endometriosis, can enable the variants of the disclosure to be used to develop superior diagnostic tests capable of identifying individuals who express a detectable trait, such as endometriosis. as the result of a specific genotype, or individuals whose genotype places them at an increased or decreased risk of developing a detectable trait at a subsequent time as compared to individuals who do not have that genotype. As described herein, diagnostics may be based on a single variant or a group of variants. In some instances, combined detection of a plurality of variations, for example about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 24, 25, 30, 32, 35, 40, 45, 48, 50, 55, 60, 64, 70, 75, 80, 85, 80, 96, 100, or any other number in-between, or more, of the variants provided herein can increase the probability of an accurate diagnosis. To further increase the accuracy of diagnosis or predisposition screening, analysis of the variants of the disclosure can be combined with that of other polymorphisms or other risk factors of endometriosis, such as gender and age.

In some instances, the method herein can indicate a certain increased (or decreased) degree or likelihood of developing the endometriosis based on statistically significant association results. This information can be valuable to initiate earlier preventive treatments or to allow an individual carrying one or more significant variants or variant haplotypes to regularly scheduled physical exams to monitor for the appearance or change of their endometriosis in order to identify and begin treatment of the endometriosis at an early stage.

The diagnostic techniques herein may employ a variety of methodologies to determine whether a test subject has a variant or a variant pattern associated with an increased or decreased risk of developing a detectable trait or whether the individual suffers from a detectable trait as a result of a particular polymorphism/mutation, including, for example, methods which enable the analysis of individual chromosomes for haplotyping, family studies, single sperm DNA analysis, or somatic hybrids. The trait analyzed using the diagnostics of the disclosure may be any detectable trait that is commonly observed in pathologies and disorders related to endometriosis.

Another aspect of the disclosure relates to a method of determining whether an individual is at risk (or less at risk) of developing one or more traits or whether an individual expresses one or more traits as a consequence of possessing a particular trait-causing or trait-influencing allele. These methods generally involve obtaining a nucleic acid sample from an individual and assaying the nucleic acid sample to determine which nucleotide(s) is/are present at one or more variant positions, wherein the assayed nucleotide(s) is/are indicative of an increased or decreased risk of developing the trait or indicative that the individual expresses the trait as a result of possessing a particular trait-causing or trait-influencing allele.

The variants herein can be used to identify novel therapeutic targets for endometriosis. For example, genes containing the disease-associated variants (“variant genes”) or their products, as well as genes or their products that are directly or indirectly regulated by or interacting with these variant genes or their products, can be targeted for the development of therapeutics that, for example, treat the endometriosis or prevent or delay endometriosis onset. The therapeutics may be composed of, for example, small molecules, proteins, protein fragments or peptides, antibodies, nucleic acids, or their derivatives or mimetics which modulate the functions or levels of the target genes or gene products.

The variants/haplotypes herein can be useful for improving many different aspects of the drug development process. For example, individuals can be selected for clinical trials based on their variant genotype. Individuals with variant genotypes that indicate that they are most likely to respond to or most likely to benefit from a device or a drug can be included in the trials and those individuals whose variant genotypes indicate that they are less likely to or would not respond to a device or a drug, or suffer adverse reactions, can be eliminated from the clinical trials. This not only improves the safety of clinical trials, but also will enhance the chances that the trial will demonstrate statistically significant efficacy. Furthermore, the variants of the disclosure may explain why certain previously developed devices or drugs performed poorly in clinical trials and may help identify a subset of the population that would benefit from a drug that had previously performed poorly in clinical trials, thereby “rescuing” previously developed therapeutic treatment methods or drugs, and enabling the methods or drug to be made available to a particular endometriosis patient population that can benefit from it.

Detection Kits and Systems

In some instances, based on a variant such as SNP or indels and associated sequence information disclosed herein, detection reagents can be developed and used to assay any variant of the disclosure individually or in combination, and such detection reagents can be readily incorporated into one of the established kit or system formats which are well known in the art. The terms “kits” and “systems” can refer to such things as combinations of multiple variant detection reagents, or one or more variant detection reagents in combination with one or more other types of elements or components (e.g., other types of biochemical reagents, containers, packages such as packaging intended for commercial sale, substrates to which variant detection reagents are attached, electronic hardware components, etc.). Accordingly, the disclosure further provides variant detection kits and systems, including but not limited to, packaged probe and primer sets (e.g., TaqMan probe/primer sets), arrays/microarrays of nucleic acid molecules, and beads that contain one or more probes, primers, or other detection reagents for detecting one or more variants of the disclosure. The kits/systems can optionally include various electronic hardware components; for example, arrays (“DNA chips”) and microfluidic systems (“lab-on-a-chip” systems) provided by various manufacturers typically comprise hardware components. Other kits/systems (e.g., probe/primer sets) may not include electronic hardware components, but may be comprised of, for example, one or more variant detection reagents (along with, optionally, other biochemical reagents) packaged in one or more containers.

In some instances, provided herein is a kit comprising one or more variant detection agents, and methods for detecting the variants disclosed herein by employing detection reagents and optionally a questionnaire of non-genetic clinical factors. In some instances, provided herein is a method of identifying an individual having an increased or decreased risk of developing endometriosis by detecting the presence or absence of a variant allele disclosed herein. In some instances, provided herein is a method for diagnosis of endometriosis by detecting the presence or absence of a variant allele disclosed herein is provided. In some instances, provided herein is a method for predicting endometriosis sub-classification by detecting the presence or absence of a variant allele. In some instances, the questionnaire would be completed by a medical professional based on medical history physical exam or other clinical findings. In some instances, the questionnaire would include any other non-genetic clinical factors known to be associated with the risk of developing endometriosis. In some instances, a reagent for detecting a variant in the context of its naturally-occurring flanking nucleotide sequences (which can be, e.g., either DNA or mRNA) is provided. In some instances, the reagent may be in the form of a hybridization probe or an amplification primer that is useful in the specific detection of a variant of interest. In some instances, a variant can be a genetic polymorphism having a Minor Allele Frequency (MAF) of at least 1% in a population (such as for instance the Caucasian population or the CEU population) and an RV is understood to be a genetic polymorphism having a Minor Allele Frequency (MAF) of less than 1% in a population (such as for instance the Caucasian population or the CEU population).

In some instances, a detection kit can contain one or more detection reagents and other components (e.g., a buffer, enzymes such as DNA polymerases or ligases, chain extension nucleotides such as deoxynucleotide triphosphates, and in the case of Sanger-type DNA sequencing reactions, chain terminating nucleotides, positive control sequences, negative control sequences, and the like) necessary to carry out an assay or reaction, such as amplification and/or detection of a variant-containing nucleic acid molecule. A kit may further contain means for determining the amount of a target nucleic acid, and means for comparing the amount with a standard, and can comprise instructions for using the kit to detect the variant-containing nucleic acid molecule of interest. In one embodiment of the disclosure, kits are provided which contain the necessary reagents to carry out one or more assays to detect one or more variants disclosed herein. In an exemplary embodiment of the disclosure, the detection kits/systems can be in the form of nucleic acid arrays, or compartmentalized kits, including microfluidic/lab-on-a-chip systems.

In some instances, variant detection kits/systems may contain, for example, one or more probes, or pairs of probes, that hybridize to a nucleic acid molecule at or near each target variant position. Multiple pairs of allele-specific probes may be included in the kit/system to simultaneously assay large numbers of variants, at least one of which is a variant of the disclosure. In some kits/systems, the allele-specific probes are immobilized to a substrate such as an array or bead. For example, the same substrate can comprise allele-specific probes for detecting at least 1; 10; 100; 1000; 10,000; 100,000; 500,000 (or any other number in-between) or substantially all of the variants disclosed herein.

The terms “arrays,” “microarrays,” and “DNA chips” are used herein interchangeably to refer to an array of distinct polynucleotides affixed to a substrate, such as glass, plastic, paper, nylon or other type of membrane, filter, chip, or any other suitable solid support. The polynucleotides can be synthesized directly on the substrate, or synthesized separate from the substrate and then affixed to the substrate.

In some instances, any number of probes, such as allele-specific probes, may be implemented in an array, and each probe or pair of probes can hybridize to a different variant position. In the case of polynucleotide probes, they can be synthesized at designated areas (or synthesized separately and then affixed to designated areas) on a substrate using a light-directed chemical process. Each DNA chip can contain, for example, thousands to millions of individual synthetic polynucleotide probes arranged in a grid-like pattern and miniaturized (e.g., to the size of a dime). For example, probes are attached to a solid support in an ordered, addressable array.

In some instances, a microarray can be composed of a large number of unique, single-stranded polynucleotides fixed to a solid support. Typical polynucleotides are for example about 6-60 nucleotides in length, more for example about 15-30 nucleotides in length, and most for example about 18-25 nucleotides in length. For certain types of microarrays or other detection kits/systems, it may be suitable to use oligonucleotides that are only about 7-20 nucleotides in length. In other types of arrays, such as arrays used in conjunction with chemiluminescent detection technology, exemplary probe lengths can be, for example, about 15-80 nucleotides in length, for example about 50-70 nucleotides in length, more for example about 55-65 nucleotides in length, and most for example about 60 nucleotides in length. The microarray or detection kit can contain polynucleotides that cover the known 5′ or 3′ sequence of the target variant site, sequential polynucleotides that cover the full-length sequence of a gene/transcript; or unique polynucleotides selected from particular areas along the length of a target gene/transcript sequence, particularly areas corresponding to one or more variants disclosed herein. Polynucleotides used in the microarray or detection kit can be specific to a variant or variants of interest (e.g., specific to a particular SNP allele at a target SNP site, or specific to particular SNP alleles at multiple different SNP sites), or specific to a polymorphic gene/transcript or genes/transcripts of interest.

In some instances, hybridization assays based on polynucleotide arrays rely on the differences in hybridization stability of the probes to perfectly matched and mismatched target sequence variants. For variant genotyping, it is generally suitable that stringency conditions used in hybridization assays are high enough such that nucleic acid molecules that differ from one another at as little as a single variant position can be differentiated (e.g., typical variant hybridization assays are designed so that hybridization will occur only if one particular nucleotide is present at a variant position, but will not occur if an alternative nucleotide is present at that variant position). Such high stringency conditions may be suitable when using, for example, nucleic acid arrays of allele-specific probes for variant detection. In some instances, the arrays are used in conjunction with chemiluminescent detection technology.

In some instances, a nucleic acid array can comprise an array of probes of about 15-25 nucleotides in length. In further embodiments, a nucleic acid array can comprise any number of probes, in which at least one probe is capable of detecting one or more variants disclosed herein and/or at least one probe comprises a fragment of one of the sequences selected from the group consisting of those disclosed herein, and sequences complementary thereto, said fragment comprising at least about 8 consecutive nucleotides, for example 10, 12, 15, 16, 18, 20, more for example 22, 25, 30, 40, 47, 50, 55, 60, 65, 70, 80, 90, 100, or more consecutive nucleotides (or any other number in-between) and containing (or being complementary to) a variant. In some embodiments, the nucleotide complementary to the variant site is within 5, 4, 3, 2, or 1 nucleotide from the center of the probe, more for example at the center of said probe.

In some instances, using such arrays or other kits/systems, the disclosure provides methods of identifying the variants disclosed herein in a test sample. Such methods typically involve incubating a test sample of nucleic acids with an array comprising one or more probes corresponding to at least one variant position of the disclosure, and assaying for binding of a nucleic acid from the test sample with one or more of the probes. Conditions for incubating a variant detection reagent (or a kit/system that employs one or more such variant detection reagents) with a test sample vary. Incubation conditions depend on such factors as the format employed in the assay, the detection methods employed, and the type and nature of the detection reagents used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification and array assay formats can readily be adapted to detect the variants disclosed herein.

In some instances, a detection kit/system may include components that are used to prepare nucleic acids from a test sample for the subsequent amplification and/or detection of a variant-containing nucleic acid molecule. Such sample preparation components can be used to produce nucleic acid extracts, including DNA and/or RNA, extracts from any bodily fluids. In an exemplary embodiment of the disclosure, the bodily fluid is blood, saliva or buccal swabs. The test samples used in the above-described methods will vary based on such factors as the assay format, nature of the detection method, and the specific tissues, cells or extracts used as the test sample to be assayed. Methods of preparing nucleic acids are well known in the art and can be readily adapted to obtain a sample that is compatible with the system utilized. In some instances, in addition to reagents for preparation of nucleic acids and reagents for detection of one of the variants of this disclosure, the kit may include a questionnaire inquiring about non-genetic clinical factors such as age, gender, or any other non-genetic clinical factors known to be associated with endometriosis.

In some instances, a form of kit can be a compartmentalized kit. A compartmentalized kit includes any kit in which reagents are contained in separate containers. Such containers include, for example, small glass containers, plastic containers, strips of plastic, glass or paper, or arraying material such as silica. Such containers allow one to efficiently transfer reagents from one compartment to another compartment such that the test samples and reagents are not cross-contaminated, or from one container to another vessel not included in the kit, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another or to another vessel. Such containers may include, for example, one or more containers which will accept the test sample, one or more containers which contain at least one probe or other variant detection reagent for detecting one or more variants of the disclosure, one or more containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and one or more containers which contain the reagents used to reveal the presence of the bound probe or other variant detection reagents. The kit can optionally further comprise compartments and/or reagents for, for example, nucleic acid amplification or other enzymatic reactions such as primer extension reactions, hybridization, ligation, electrophoresis (for example capillary electrophoresis), mass spectrometry, and/or laser-induced fluorescent detection. The kit may also include instructions for using the kit. In such microfluidic devices, the containers may be referred to as, for example, microfluidic “compartments”, “chambers”, or “channels”.

In some instances, microfluidic devices, which may also be referred to as “lab-on-a-chip” systems, biomedical micro-electro-mechanical systems (bioMEMs), or multicomponent integrated systems, are exemplary kits/systems of the disclosure for analyzing variants. Such systems miniaturize and compartmentalize processes such as probe/target hybridization, nucleic acid amplification, and capillary electrophoresis reactions in a single functional device. Such microfluidic devices typically utilize detection reagents in at least one aspect of the system, and such detection reagents may be used to detect one or more variants of the disclosure. One example of a microfluidic system is the integration of PCR amplification and capillary electrophoresis in chips. Exemplary microfluidic systems comprise a pattern of microchannels designed onto a glass, silicon, quartz, or plastic wafer included on a microchip. The movements of the samples may be controlled by electric, electroosmotic or hydrostatic forces applied across different areas of the microchip to create functional microscopic valves and pumps with no moving parts. Varying the voltage can be used as a means to control the liquid flow at intersections between the micro-machined channels and to change the liquid flow rate for pumping across different sections of the microchip. In some instances, for genotyping variants, a microfluidic system may integrate, for example, nucleic acid amplification, primer extension, capillary electrophoresis, and a detection method such as laser induced fluorescence detection.

Detection Kits and Systems

In some instances, based on a variant, detection reagents can be developed and used to assay any variant of the disclosure individually or in combination, and such detection reagents can be readily incorporated into one of the established kit or system formats which are well known in the art. The terms “kits” and “systems” can refer to such things as combinations of multiple variant detection reagents, or one or more variant detection reagents in combination with one or more other types of elements or components (e.g., other types of biochemical reagents, containers, packages such as packaging intended for commercial sale, substrates to which variant detection reagents are attached, electronic hardware components, etc.). Accordingly, the disclosure further provides variant detection kits and systems, including but not limited to, packaged probe and primer sets (e.g., TaqMan probe/primer sets), arrays/microarrays of nucleic acid molecules, and beads that contain one or more probes, primers, or other detection reagents for detecting one or more variants of the disclosure. The kits/systems can optionally include various electronic hardware components; for example, arrays (“DNA chips”) and microfluidic systems (“lab-on-a-chip” systems) provided by various manufacturers may comprise hardware components. Other kits/systems (e.g., probe/primer sets) may not include electronic hardware components, but may be comprised of, for example, one or more variant detection reagents (along with, optionally, other biochemical reagents) packaged in one or more containers.

Methods of Treatment

In some aspects, disclosed herein is a method of treating a select subject in need thereof. The use of these genetic markers can allow selection of subjects for clinical trials involving novel treatment methods. In some cases, genetic markers disclosed herein can be used for early diagnosis and prognosis of endometriosis, as well as early clinical intervention to mitigate progression of the disease. In some instances, genetic markers disclosed herein can be used to predict endometriosis and endometriosis progression, for example in treatment decisions for individuals who are recognized as having endometriosis.

In some cases, a treatment disclosed herein includes one or more of: reducing the frequency and/or severity of symptoms, elimination of symptoms and/or their underlying cause, and improvement or remediation of damage. For example, treatment of endometriosis includes, relieving the pain experienced by a woman suffering from endometriosis, and/or causing the regression or disappearance of endometriotic lesions.

In some cases, the treatment can be an advanced reproductive technology therapy such as in vitro in fertilization (IVF); a hormonal treatment; progestogen; progestin; an oral contraceptive; a hormonal contraceptive; danocrine; gentrinone; a gonadotrophin releasing hormone agonist; Lupron; danazol; an aromatase inhibitor; pentoxifylline; surgical treatment; laparoscopy; cauterization; or cystectomy. In some instances, the progestogen can be progesterone, desogestrel, etonogestrel, gestodene, levonorgestrel, medroxyprogesterone, norethisterone, norgestimate, megestrol, megestrol acetate, norgestrel, a pharmaceutically acceptable salt thereof (e.g., acetate), or any combination thereof. In some instances, a therapeutic used herein is selected from progestins, estrogens, antiestrogens, and antiprogestins, for example micronized danazol in a micro- or nanoparticulate formulation.

In some cases, a method of treatment disclosed herein comprises direct administration into or within an endometriotic lesion in a subject suffering from endometriosis of a pharmaceutical composition comprising a therapeutic disclosed herein. In some instances, the therapeutic is micronized in a suspension, e.g., non-oil based suspension. In some embodiments, the suspension comprises water, sodium sulfate, a quaternary ammonium wetting agent, glycerol, propylene glycol, polyethylene glycol, polypropylene glycol, a hydrophilic colloid, or any combination thereof.

The term “effective amount,” as used herein, can refer to a sufficient amount of a therapeutic being administered which relieve to some extent one or more of the symptoms of the disease or condition being treated. The result can be reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. A therapeutic can be administered for prophylactic, enhancing, and/or therapeutic treatments. An appropriate “effective” amount in any individual case can be determined using techniques, such as a dose escalation study.

A treatment can comprise administering a therapeutic to a subject, intralesionally, transvaginally, intravenously, subcutaneously, intramuscularly, by inhalation, dermally, intra-articular injection, orally, intrathecally, transdermally, intranasally, via a peritoneal route, or directly onto or into a lesion/site, e.g., via endoscopically, open surgical administration, or injection route of application. In some instances, intralesional administration can mean administration into or within a pathological area. Administration can be effected by injection into a lesion and/or by instillation into a pre-existing cavity, such as in endometrioma. With reference to treatments for endometriosis provided herein, intralesional administration can refer to treatment within endometriotic tissue or a cyst formed by such tissue, such as by injection into a cyst. In some instances, intralesional administration can include administration into tissue in such close proximity to the endometriotic tissue such that the progestogen acts directly on the endometriotic tissue. In some instances, intralesional administration may or may not include administration to tissue remote from the endometriotic tissue that the progestogen acts on the endometriotic tissue through systemic circulation. In some instances, intralesional administration or delivery includes transvaginal, endoscopic or open surgical administration including, but are not limited to, via laparotomy. In some instances, transvaginal administration can refer to all procedures, including drug delivery, performed through the vagina, including intravaginal delivery and transvaginal sonography (ultrasonography through the vagina).

In some instances, administration is by injection into the endometriotic tissue or into a cyst formed by such tissue; or into tissue immediately surrounding the endometriotic tissue in such proximity that the progestogen acts directly on the endometriotic tissue. In some embodiments, the tissue is visualized, for example laparoscopically or by ultrasound, and the progestogen is administered by intralesional (intracystic) injection by, for example direct visualization under ultrasound guidance or by any other suitable methods. A suitable amount of the therapeutic, e.g., progestrogen expressed in terms of progesterone of about 1-2 gm per lesion/cyst, can be applied. Precise quantity generally is determined on case to case basis, depending upon parameters, such as the size of the endometriotic tissue mass, the mode of the administration, and the number and time intervals between treatments.

In some instances, methods herein can comprise intralesional delivery of the medicaments into the lesion. Intralesional delivery includes, for example, transvaginal, endoscopic or open surgical administration including via laparotomy. Delivery can be effected, for example, through a needle or needle like device by injection or a similar injectable or syringe-like device that can be delivered into the lesion, such as transvaginally, endoscopically or by open surgical administration including via laparotomy. In some embodiments, the method includes intravaginal and transvaginal delivery. For intravaginal/transvaginal delivery an ultrasound probe can be used to guide delivery of the needle from the vagina into lesions such as endometriomas and utero sacral nodules. Under ultrasound guidance the needle tip is placed in the lesion, the contents of the lesion aspirated if necessary and the formulation is injected into the lesion. In an exemplary delivery system a 17 to 20 gauge needle can be used for injection of the drug. Such system can be used for intralesional delivery including, but not limited to, transvaginal, endoscopic or open surgical administration including via laparotomy. For treatment of endometrioma 17 or 18 gauge needles are used under ultrasound guidance for aspiration of the thick contents of the lesion and delivery of the formulation. The length of the needle used depends on the depth of the lesion. Pre-loaded syringes and other administration systems, which obviate the need for reloading the drug can be used.

In some cases, a therapeutic (e.g., an active agent) used herein can be a solution, a suspension, liquid, a paste, aqueous, non-aqueous fluid, semi-solids, colloid, gel, lotion, cream, solid (e.g., tablet, powder, pellet, particulate, capsule, packet), or any combination thereof. In some instances, a therapeutic disclosed herein is formulated as a dosage form of tablet, capsule, gel, lollipop, parenteral, intraspinal infusion, inhalation, spray, aerosol, transdermal patch, iontophoresis transport, absorbing gel, liquid, liquid tannate, suppositories, injection, I.V. drip, or a combination thereof to treat subjects. In some instances, the active agents are formulated as single oral dosage form such as a tablet, capsule, cachet, soft gelatin capsule, hard gelatin capsule, extended release capsule, tannate tablet, oral disintegrating tablet, multi-layer tablet, effervescent tablet, bead, liquid, oral suspension, chewable lozenge, oral solution, lozenge, lollipop, oral syrup, sterile packaged powder including pharmaceutically-acceptable excipients, other oral dosage forms, or a combination thereof. In some instances, a therapeutic of the disclosure herein can be administered using one or more different dosage forms which are further disclosed herein. In some instances, therapeutics disclosed herein are provided in modified release dosage forms (such as immediate release, controlled release, or both),

The methods, compositions, and kits of this disclosure can comprise a method to prevent, treat, arrest, reverse, or ameliorate the symptoms of a condition of a subject, e.g., a patient. A subject can be, for example, an elderly adult, adult, adolescent, pre-adolescence, teenager, or child. A subject can be, for example, 10-50 years old, 10-40 years old, 10-30 years old, 10-25 years old, 10-21 years old, 10-18 years old, 10-16 years old, 18-25 years old, or 16-34 years old. The subject can be a female mammal, e.g., a female human being. In some instances, the human subject can be asymptomatic for endometriosis.

Treatment can be provided to the subject before clinical onset of disease. Treatment can be provided to the subject after clinical onset of disease. Treatment can be provided to the subject after 1 day, 1 week, 6 months, 12 months, or 2 years or more after clinical onset of the disease. Treatment may be provided to the subject for more than 1 day, 1 week, 1 month, 6 months, 12 months, 2 years or more after clinical onset of disease. Treatment may be provided to the subject for less than 1 day, 1 week, 1 month, 6 months, 12 months, or 2 years after clinical onset of the disease. Treatment can also include treating a human in a clinical trial.

A treatment, e.g., administration of a therapeutic, can occur 1, 2, 3, 4, 5, 6, 7, or 8 times daily. A treatment, e.g., administration of a therapeutic, can occur 1, 2, 3, 4, 5, 6, or 7 times weekly. A treatment, e.g., administration of a therapeutic, can occur 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times monthly. A treatment, e.g., administration of a therapeutic, can occur 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 times yearly. In some instances, therapeutics disclosed herein are administered to a subject at about every 4 to about 6 hours, about every 12 hours, about every 24 hours, about every 48 hours, or more often. In some instances, therapeutics disclosed herein can be administered once, twice, three times, four times, five times, six times, seven times, eight times, or more often daily. In some instances, a dosage form disclosed herein provides an effective plasma concentration of an active agent at from about 1 minute to about 20 minutes after administration, such as about: 2 min, 3 min, 4 min, 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min. In some instances, a dosage form of the disclosure herein provides an effective plasma concentration of an active agent at from about 20 minutes to about 24 hours after administration, such as about 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hr, 1.2 hrs, 1.4 hrs, 1.6 hrs, 1.8 hrs, 2 hrs, 2.2 hrs, 2.4 hrs, 2.6 hrs, 2.8 hrs, 3 hrs, 3.2 hrs, 3.4 hrs, 3.6 hrs, 3.8 hrs, 4 hrs, 5 hrs, 6 hrs, 7 hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs, 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs, 17 hrs, 18 hrs, 19 hrs, 20 hrs, 21 hrs, 22 hrs, 23 hrs, or 24 hrs following administration. In some instances, an active agent can be present in an effective plasma concentration in a subject for about 4 to about 6 hours, about 12 hours, about 24 hour, or 1 day to 30 days, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days.

In some instances, a therapeutic (e.g., an active agent) is administered to a subject in a dosage of about 0.01 mg to about 500 mg per day, e.g., about 1-50 mg/day for an average person. In some embodiments, the daily dosage is from about 0.01 mg to about 5 mg, about 1 to about 10 mg, about 5 mg to about 20 mg, about 10 mg to about 50 mg, about 20 mg to about 100 mg, about 50 mg to about 150 mg, about 100 mg to about 250 mg, about 150 mg to about 300 mg, or about 250 mg to about 500 mg.

In some instances, each administration of a therapeutic (e.g., an active agent) is in an amount of about: 0.1-5 mg, 0.1-10 mg, 1-5 mg, 1-10 mg, 1-20 mg, 10-20 mg, 10-30 mg, 10-40 mg, 10-50 mg, 20-30 mg, 20-40 mg, 20-50 mg, 25-50 mg, 30-40 mg, 30-50 mg, 30-60 mg, 40-50 mg, 40-60 mg, 50-60 mg, 50-75 mg, 60-80 mg, 75-100 mg, or 80-100 mg, for example: about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg, about 9 mg, about 9.5 mg, about 10 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, about 15 mg, about 15.5 mg, about 16 mg, about 16.5 mg, about 17 mg, about 17.5 mg, about 18 mg, about 18.5 mg, about 19 mg, about 19.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27.5 mg, about 30 mg, about 32.5 mg, about 35 mg, about 37.5 mg, about 40 mg, about 42.5 mg, about 45 mg, about 47.5 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg.

In some instances, a therapeutic (e.g., an active agent) is administered to a subject in a dosage of about 0.01 g to about 100 g per day, e.g., about 1-10 g/day for an average person. In some embodiments, the daily dosage is from about 0.01 g to about 5 g, about 1 to about 10 g, about 5 g to about 20 g, about 10 g to about 50 g, about 20 g to about 100 g, or about 50 g to about 100 g.

In some instances, each administration of a therapeutic (e.g., an active agent) is in an amount of about: 0.01-1 g, 0.1-5 g, 0.1-10 g, 1-5 g, 1-10 g, 1-20 g, 10-20 g, 10-30 g, 10-40 g, 10-50 g, 20-30 g, 20-40 g, 20-50 g, 25-50 g, 30-40 g, 30-50 g, 30-60 g, 40-50 g, 40-60 g, 50-60 g, 50-75 g, 60-80 g, 75-100 g, or 80-100 g, for example: about 0.5 g, about 1 g, about 1.5 g, about 2 g, about 2.5 g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, about 5 g, about 5.5 g, about 6 g, about 6.5 g, about 7 g, about 7.5 g, about 8 g, about 8.5 g, about 9 g, about 9.5 g, about 10 g, about 10.5 g, about 11 g, about 11.5 g, about 12 g, about 12.5 g, about 13 g, about 13.5 g, about 14 g, about 14.5 g, about 15 g, about 15.5 g, about 16 g, about 16.5 g, about 17 g, about 17.5 g, about 18 g, about 18.5 g, about 19 g, about 19.5 g, about 20 g, about 22.5 g, about 25 g, about 27.5 g, about 30 g, about 32.5 g, about 35 g, about 37.5 g, about 40 g, about 42.5 g, about 45 g, about 47.5 g, about 50 g, about 55 g, about 60 g, about 65 g, about 70 g, about 75 g, about 80 g, about 85 g, about 90 g, about 95 g, or about 100 g.

In some instances, a therapeutic (e.g., in a liquid) administered to a subject having an active agent concentration of about: 0.01-0.1, 0.1-1, 1-10, 1-20, 5-30, 5-40, 5-50, 10-20, 10-25, 10-30, 10-40, 10-50, 15-20, 15-25, 15-30, 15-40, 15-50, 20-30, 20-40, 20-50, 20-100, 30-40, 30-50, 30-60, 30-70, 30-80, 30-90, 30-100, 40-50, 40-60, 40-70, 40-80, 40-90, 40-100, 50-60, 50-70, 50-80, 50-90, 50-100, 50-150, 50-200, 50-300, 100-300, 100-400, 100-500, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 μM, or any combination thereof.

In some cases, a therapeutic can comprise one or more active agents, administered to a subject at least about: 0.001 mg, 0.01 mg, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, or 10 mg, or per kg body weight of a subject in need thereof. The therapeutic may comprise a total dose of one or more active agents administered at about 0.1 to about 10.0 mg, for example, about 0.1-10.0 mg, about 0.1-9.0 mg, about 0.1-8.0 mg, about 0.1-7.0 mg, about 0.1-6.0 mg, about 0.1-5.0 mg, about 0.1-4.0 mg, about 0.1-3.0 mg, about 0.1-2.0 mg, about 0.1-1.0 mg, about 0.1-0.5 mg, about 0.2-10.0 mg, about 0.2-9.0 mg, about 0.2-8.0 mg, about 0.2-7.0 mg, about 0.2-6.0 mg, about 0.2-5.0 mg, about 0.2-4.0 mg, about 0.2-3.0 mg, about 0.2-2.0 mg, about 0.2-1.0 mg, about 0.2-0.5 mg, about 0.5-10.0 mg, about 0.5-9.0 mg, about 0.5-8.0 mg, about 0.5-7.0 mg, about 0.5-6.0 mg, about 0.5-5.0 mg, about 0.5-4.0 mg, about 0.5-3.0 mg, about 0.5-2.0 mg, about 0.5-1.0 mg, about 1.0-10.0 mg, about 1.0-5.0 mg, about 1.0-4.0 mg, about 1.0-3.0 mg, about 1.0-2.0 mg, about 2.0-10.0 mg, about 2.0-9.0 mg, about 2.0-8.0 mg, about 2.0-7.0 mg, about 2.0-6.0 mg, about 2.0-5.0 mg, about 2.0-4.0 mg, about 2.0-3.0 mg, about 5.0-10.0 mg, about 5.0-9.0 mg, about 5.0-8.0 mg, about 5.0-7.0 mg, about 5.0-6.0 mg, about 6.0-10.0 mg, about 6.0-9.0 mg, about 6.0-8.0 mg, about 6.0-7.0 mg, about 7.0-10.0 mg, about 7.0-9.0 mg, about 7.0-8.0 mg, about 8.0-10.0 mg, about 8.0-9.0 mg, or about 9.0-10.0 mg, or per kg body weight of a subject in need thereof.

In some cases, a method of treatment disclosed herein comprises administering a therapeutic. In some instances, the method comprises administering a therapeutic includes one or more of the following steps: a) obtaining a genetic material sample of a human female subject, b) identifying in the genetic material of the subject a genetic marker having an association with endometriosis, c) assessing the subject's risk of endometriosis or risk of endometriosis progression, d) identifying the subject as having an altered risk of endometriosis or an altered risk of endometriosis progression, e) administering to the subject a therapeutic, or any combination thereof.

In some instances, the subject may be endometriosis presymptomatic or the subject may exhibit endometriosis symptoms. In some instances, the assessment of risk may include non-genetic clinical factors. In some instances, the therapeutic is adapted to the specific subject so as to be a proper and effective amount of therapeutic for the subject. In some instances, the administration of the therapeutic may comprise multiple sequential instances of administration of the therapeutic and that such sequence instances may occur over an extended period of time or may occur on an indefinite on-going basis. In some instances, the therapeutic may be a gene or protein based therapy adapted to the specific needs of a select patient.

Hormonal Therapy

In some cases, a treatment method herein comprises supplementing the body with a hormone thereof such as a steroid hormone, for example a method of preventing endometriosis comprising administering a hormonal therapy to a human subject having at least one genetic variant defining a minor allele disclosed herein, e.g., listed in Table 1. In some instances, the hormone can be progestin, progestogen, progesterone, desogestrel, etonogestrel, gestodene, levonorgestrel, medroxyprogesterone, norethisterone, norgestimate, megestrol, megestrol acetate, norgestrel, a pharmaceutically acceptable salt thereof (e.g., acetate), or any combination thereof. In some instances, a therapeutic used herein is selected from progestins, estrogens, antiestrogens, and antiprogestins, for example micronized danazol in a micro- or nanoparticulate formulation. Methods and therapeutics presented herein can utilize an active agent in a freebase, salt, hydrate, polymorph, isomer, diastereomer, prodrug, metabolite, ion pair complex, or chelate form. An active agent can be formed using a pharmaceutically acceptable non-toxic acid or base, including an inorganic acid or base, or an organic acid or base. In some instances, an active agent that can be utilized in connection with the methods and compositions presented herein is a pharmaceutically acceptable salt derived from acids including, but not limited to, the following: acetic, alginic, anthranilic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethenesulfonic, formic, fumaric, furoic, galacturonic, gluconic, glucuronic, glutamic, glycolic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phenylacetic, phosphoric, propionic, salicylic, stearic, succinic, sulfanilic, sulfuric, tartaric acid, or p-toluenesulfonic acid. For further description of pharmaceutically acceptable salts that can be used in the methods described herein see, for example, S. M. Barge et al., “Pharmaceutical Salts,” 1977, J. Pharm. Sci. 66:1-19, which is incorporated herein by reference in its entirety.

In some instances, the therapeutic may take the form of a testosterone or a modified testosterone such as Danazol. In some instances, the therapeutic can be a hormonal treatment therapeutic which may be administered alone or in combination with a gene therapy. For instance, the therapeutic may be an estrogen containing composition, a progesterone containing composition, a progestin containing composition, a gonadotropin releasing-hormone (GnRH) agonist, a gonadotropin releasing-hormone (GnRH) antagonist, or other ovulation suppression composition, or a combination thereof. In some instances, the GnRH agonist may take the form of a GnRH agonist in combination with a patient specific substantially low dose of estrogen, progestin, or tibolone via an add-back administration. In some instances, in such add-back therapy, the dosage of estrogen, progestin, or tibolone is relatively small so as to not reduce the effectiveness of the GnRH agonist. In some instances, the therapeutic is an oral contraceptive (OC). In some instances, the OC is in a pill form that is comprised at least partially of estrogen, progesterone, or a combination thereof. In some instances, the progesterone component may be any of Desogestrel, Drospirenone, Ethynodiol, Levonorgestrel, Norethindrone, Norgestimate, and Norgestrel, and the estrogen component may further be any of Mestranol, Estradiol, and Ethinyl. In some instances, the OC may be any commercially available OC including ALESSE, APRI, ARANELLE, AVIANE, BREVICON, CAMILA, CESIA, CRYSELLE, CYCLESSA, DEMULEN, DESOGEN, ENPRESSE, ERRIN, ESTROSTEP, JOLIVETTE, JUNEL, KARIVA, LEENA, LESSINA, LEVLEN, LEVORA, LOESTRIN, LUTERA, MICROGESTIN, MICRONOR, MIRCETTE, MODICON, MONONESSA, NECON, NORA, NORDETTE, NORINYL, NOR-QD, NORTREL, OGESTREL, ORTHO-CEPT, ORTHO-CYCLEN, ORTHO-NOVUM, ORTHO-TRI-CYCLEN, OVCON, OVRAL, OVRETTE, PORTIA, PREVIFEM, RECLIPSEN, SOLIA, SPRINTEC, TRINESSA, TRI-NORINYL, TRIPHASIL, TRIVORA, VELIVET, YASMIN, AND ZOVIA (the preceding names are the registered trademarks of the respective providers).

Assisted Reproductive Technology Therapy

In some cases, a method herein can comprise administering to a select subject assisted reproductive technology therapy (ART), for example a method of treating endometriosis-associated infertility comprising administering ART to a select human subject having at least one genetic variant defining a minor allele disclosed herein, e.g., listed in Table 2. In some instances, ART can comprise in vitro fertilization (IVF), embryo transfer (ET), fertility medication, intracytoplasmic sperm injection (ICSI), cryopreservation, or any combination thereof. In some instances, ART can comprise surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman.

In some cases, assisted reproductive technology therapy can comprises all treatments or procedures that include the handling of human eggs or embryos to help a woman become pregnant. For example, in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), tubal embryo transfer, gg and embryo cryopreservation, egg and embryo donation and gestational surrogacy.

In some instances, the in vitro fertilization (IVF) procedure can provide for a live birth event following the IVF procedure. In some instances, a method herein provides a probability of a live birth event occurring resulting from the first or subsequent in vitro fertilization cycle based at least in part on items of information from the female subjects.

In some instances, the IVF can comprise ovulation induction, utilizing fertility medication can comprise agents that stimulate the development of follicles in the ovary. Examples are gonadotropins and gonadotropin releasing hormone.

In some instances, IVF can comprise transvaginal ovum retrieval (OVR), which can be a process whereby a small needle is inserted through the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid that contains the eggs.

In some instances, IVF can comprise embryo transfer, which can be the step in the process whereby one or several embryos are placed into the uterus of the female with the intent to establish a pregnancy.

In some instances, IVF can comprise assisted zona hatching (AZH), which can be performed shortly before the embryo is transferred to the uterus. A small opening can be made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo.

In some instances, IVF can comprise artificial insemination, for example intrauterine insemination, intracervical insemination, intrauterine tuboperitoneal insemination, intratubal insemination, or any combination thereof.

In some instances, IVF can comprise intracytoplasmic sperm injection (ICSI), which can be beneficial in the case of male factor infertility where sperm counts are very low or failed fertilization occurred with previous IVF attempt(s). The ICSI procedure can involve a single sperm carefully injected into the center of an egg using a microneedle. With IC SI, only one sperm per egg is needed. Without ICSI, one may need between 50,000 and 100,000. In some embodiments, this method can be employed when donor sperm is used.

In some instances, IVF can comprise autologous endometrial coculture, which can be a possible treatment for patients who have failed previous IVF attempts or who have poor embryo quality. The patient's fertilized eggs can be placed on top of a layer of cells from the patient's own uterine lining, creating a more natural environment for embryo development.

In some instances, IVF can comprise zygote intrafallopian transfer (ZIFT), in which egg cells can be removed from the woman's ovaries and fertilized in the laboratory; the resulting zygote can be then placed into the fallopian tube.

In some instances, IVF can comprise cytoplasmic transfer, in which the contents of a fertile egg from a donor can be injected into the infertile egg of the patient along with the sperm.

In some instances, IVF can comprise egg donors, which are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age. In the egg donor process, eggs can be retrieved from a donor's ovaries, fertilized in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos can be returned to the recipient's uterus.

In some instances, IVF can comprise sperm donation, which may provide the source for the sperm used in IVF procedures where the male partner produces no sperm or has an inheritable disease, or where the woman being treated has no male partner.

In some instances, IVF can comprise preimplantation genetic diagnosis (PGD), which can involve the use of genetic screening mechanisms such as fluorescent in-situ hybridization (FISH) or comparative genomic hybridization (CGH) to help identify genetically abnormal embryos and improve healthy outcomes.

In some instances, IVF can comprise embryo splitting can be used for twinning to increase the number of available embryos.

In some instances, ART can comprise gamete intrafallopian transfer (GIFT), in which a mixture of sperm and eggs can be placed directly into a woman's fallopian tubes using laparoscopy following a transvaginal ovum retrieval.

In some instances, ART can comprise reproductive surgery, treating e.g. fallopian tube obstruction and vas deferens obstruction, or reversing a vasectomy by a reverse vasectomy. In surgical sperm retrieval (SSR) the reproductive urologist can obtain sperm from the vas deferens, epididymis or directly from the testis in a short outpatient procedure. By cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVF.

In some instances, a subject to treat can be a pre-in vitro fertilization (pre-IVF) procedure patient. In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a pre-IVF procedure patient may include age, diminished ovarian reserve, 3 follicle stimulating hormone (FSH) level, body mass index, polycystic ovarian disease, season, unexplained female infertility, number of spontaneous miscarriages, year, other causes of female infertility, number of previous pregnancies, number of previous term deliveries, endometriosis, tubal disease, tubal ligation, male infertility, uterine fibroids, hydrosalpinx, and male infertility causes.

In some instances, a subject to treat can be a pre-surgical (pre-OR) procedure patient (pre-OR is also referred to herein as pre-oocyte retrieval). In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a pre-OR procedure patient may include age, endometrial thickness, total number of oocytes, total amount of gonatropins administered, number of total motile sperm after wash, number of total motile sperm before wash, day 3 follicle stimulating hormone (FSH) level, body mass index, sperm collection, age of spouse, season number of spontaneous miscarriages, unexplained female infertility, number of previous term deliveries, year, number of previous pregnancies, other causes of female infertility, endometriosis, male infertility, tubal ligation, polycystic ovarian disease, tubal disease, sperm from donor, hydrosalpinx, uterine fibroids, and male infertility causes.

In some instances, a subject to treat can be a post-in vitro fertilization (post-IVF) procedure patient. In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a post-IVF procedure patient may include blastocyst development rate, total number of embryos, total amount of gonatropins administered, endometrial thickness, flare protocol, average number of cells per embryo, type of catheter used, percentage of 8-cell embryos transferred, day 3 follicle stimulating hormone (FSH) level, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, day of embryo transfer, season, number of spontaneous miscarriages, number of previous term deliveries, oral contraceptive pills, sperm collection, percent of unfertilized eggs, number of embryos arrested at 4-cell stage, compaction on day 3 after transfer, percent of normal fertilization, percent of abnormally fertilized eggs, percent of normal and mature oocytes, number of previous pregnancies, year, polycystic ovarian disease, unexplained female infertility, tubal disease, male infertility only, male infertility causes, endometriosis, other causes of female infertility, uterine fibroids, tubal ligation, sperm from donor, hydrosalpinx, performance of ICSI, or assisted hatching.

Pain Managing Medications

In some cases, a method disclosed herein can comprise administering a pain medication to a select subject, for example to a human subject having at least one genetic variant defining a minor allele listed in Table 3. In some instances, the pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, acetaminophen, an opioid, a cannabis-based therapeutic, or any combination thereof.

In some instances, the pain medication described herein can comprise an NSAID, for example amoxiprin, benorilate, choline magnesium salicylate, diflunisal, faislamine, methyl salicylate, magnesium salicylate, diclofenac, aceclofenac, acemetacin, bromfenac, etodolac, indometacin, nabumetone, sulindac, tolmetin, ibuprofen, carprofen, fenbuprofen, flubiprofen, ketaprofen, ketorolac, loxoprofen, naproxen, suprofen, mefenamic acid, meclofenamic acid, piroxicam, lomoxicam, meloxicam, tenoxicam, phenylbutazone, azapropazone, metamizole, oxyphenbutazone, or sulfinprazone, or a pharmaceutically acceptable salt thereof.

In some instances, the pain medication described herein can comprise an opioid analgesic, for example hydrocodone, oxycodone, morphine, diamorphine, codeine, pethidine, alfentanil, buprenorphine, butorphanol, dezocine, fentanyl, hydromorphone, levomethadyl acetate, levorphanol, meperidine, methadone, morphine sulfate, nalbuphine, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, or tramadol, or a pharmaceutically acceptable salt thereof.

In some instances, the pain medication described herein can comprise a cannabis-based therapeutic such as a cannabinoid for the treatment, reduction or prevention of pain. Exemplary cannabinoid for the treatment of pain include, without limitation, nabilone, dronabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabichromeme (CBC), cannabigerol (CBG), tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), cannabidivarin (CBDV), cannadidiolic acid (CBDA), ajulemic acid, dexanabinol, cannabinor, HU 308, HU 331, and a pharmaceutically acceptable salt thereof.

SPECIFIC EMBODIMENTS

A number of methods and systems are disclosed herein. Specific exemplary embodiments of these methods and systems are disclosed below.

Section 1 of Specific Embodiments

Embodiment 1

A method comprising: hybridizing a nucleic acid probe to a nucleic acid sample from a human subject suspected of having or developing endometriosis; and detecting a genetic variant in a panel comprising two or more genetic variants defining a minor allele listed in Table 1.

Embodiment 2

The method of embodiment 1, wherein the nucleic acid sample comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof.

Embodiment 3

The method of embodiment 1 or 2, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from cDNA or mRNA.

Embodiment 4

The method of embodiment 1 or 2, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from genomic DNA.

Embodiment 5

The method of any one of embodiments 1-4, wherein the nucleic acid probe is a sequencing primer.

Embodiment 6

The method of any one of embodiments 1-4, wherein the nucleic acid probe is an allele specific probe.

Embodiment 7

The method of any one of embodiments 1-6, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof.

Embodiment 8

The method of any one of embodiments 1-7, wherein the panel comprises at least: 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 500, or more genetic variants defining minor alleles listed in Table 1.

Embodiment 9

The method of any one of embodiments 1-8, wherein the genetic variant has an odds ratio (OR) of at least: 1.5, 2, 5, 10, 20, 50, 100, or more.

Embodiment 10

The method of any one of embodiments 1-9, wherein the genetic variant comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof.

Embodiment 11

The method of any one of embodiments 1-9, wherein the genetic variant comprises a protein damaging mutation.

Embodiment 12

The method of any one of embodiments 1-10, wherein the panel further comprises one or more protein damaging or loss of function variants in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof.

Embodiment 13

The method of embodiment 12, further comprising sequencing the one or more genes to identify the one or more protein damaging or loss of function variants.

Embodiment 14

The method of embodiment 13, wherein the one or more protein damaging or loss of function variants are identified based on a predictive computer algorithm.

Embodiment 15

The method of embodiment 13 of 14, wherein the one or more protein damaging or loss of function variants are identified based on reference to a database.

Embodiment 16

The method of any one of embodiments 12-15, wherein the one or more protein damaging or loss of function variants comprise a stop-gain mutation, a spice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof.

Embodiment 17

The method of any one of embodiments 1-16, wherein the panel further comprises one or more additional variants defining a minor allele listed in Table 4.

Embodiment 18

The method of any one of embodiments 1-17, wherein the panel is capable of identifying human subjects as having or being at risk of developing endometriosis with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 19

The method of any one of embodiments 1-18, wherein the panel is capable of identifying human subjects as having or being at risk of developing endometriosis with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 20

The method of any one of embodiments 1-19, wherein the panel is capable of identifying human subjects as having or being at risk of developing endometriosis with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 21

The method of any one of embodiments 1-20, further comprising administering a therapeutic to the human subject.

Embodiment 22

The method of embodiment 21, wherein the therapeutic comprises hormonal therapy, an advanced reproductive technology therapy, a pain managing medication, or any combination thereof.

Embodiment 23

The method of embodiment 21, wherein the therapeutic comprises hormonal contraceptives, gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn-RH) antagonists, progestin, danazol, or any combination thereof.

Embodiment 24

The method of any one of embodiments 1-23, wherein the human subject is asymptomatic for endometriosis.

Embodiment 25

The method of any one of embodiments 1-24, wherein the human subject is a teenager.

Embodiment 26

A method comprising detecting one or more genetic variants defining a minor allele listed in Table 1 in genetic material from a human subject suspected of having or developing endometriosis.

Embodiment 27

The method of embodiment 26, wherein the genetic material comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof.

Embodiment 28

The method of embodiment 26 or 27, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, of any combination thereof.

Embodiment 29

The method of any one of embodiments 26-28, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material.

Embodiment 30

The method of any one of embodiments 26-29, wherein the detecting comprises testing for the presence or absence of at least: 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, 100, 150, 250, or 500 genetic variants defining a minor allele listed in Table 1.

Embodiment 31

The method of any one of embodiments 26-30, wherein the one or more genetic variants have an odds ratio (OR) of at least: 1.5, 2, 5, 10, 20, 50, 100, or more.

Embodiment 32

The method of any one of embodiments 26-31, further comprising administering a therapeutic to the human subject.

Embodiment 33

A method comprising: sequencing one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof to identify one or more protein damaging or loss of function variants in a human subject suspected of having or developing endometriosis; and administering an endometriosis therapy to the human subject.

Embodiment 34

The method of embodiment 33, wherein the one or more protein damaging or loss of function variants are identified based on a predictive computer algorithm, reference to a database, or a combination thereof.

Embodiment 35

The method of embodiment 33 or 34, wherein the one or more protein damaging or loss of function variants comprise a stop-gain mutation, a spice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof.

Embodiment 36

The method of any one of embodiments 33-35, wherein the endometriosis therapy comprises a hormonal therapy, an assisted reproductive technology therapy, a pain medication, or any combination thereof.

Embodiment 37

A method of preventing endometriosis comprising administering a hormonal therapy to a human subject having at least one genetic variant defining a minor allele listed in Table 1.

Embodiment 38

The method of embodiment 37, wherein the hormonal therapy comprises administration of hormonal contraceptives, gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn-RH) antagonists, progestin, danazol, or any combination thereof.

Embodiment 39

A method of treating endometriosis-associated infertility comprising administering an assisted reproductive technology therapy to a human subject having at least one genetic variant defining a minor allele listed in Table 2.

Embodiment 40

The method of embodiment 39, wherein the assisted reproductive technology therapy comprises in vitro fertilization, gamete intrafallopian transfer, or any combination thereof.

The method can further comprise administering, intrauterine insemination or ovulation induction.

Embodiment 41

A method comprising administering a pain medication to a human subject having at least one genetic variant defining a minor allele listed in Table 3.

Embodiment 42

The method of embodiment 41, wherein the pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof.

Embodiment 43

The method of any one of embodiment 37-42, further comprising detecting the at least one genetic variant in a genetic material from the human subject.

Embodiment 44

The method of embodiment 43, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof.

Embodiment 45

The method of embodiment 43, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material.

Embodiment 46

The method of embodiment 45, wherein the nucleic acid probe is a sequencing primer or an allele-specific probe.

Embodiment 47

The method of any one of embodiments 37-46, wherein the at least one genetic variant has an odds ratio (OR) of at least: 1.5, 2, 5, 10, 20, 50, 100, or more.

Embodiment 48

The method of any one of embodiments 37-47, wherein the at least one genetic variant comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof.

Section 2 of Specific Embodiments

Embodiment 1

A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting one or more genetic variants in said nucleic acid sample, wherein said one or more genetic variants are listed in Table 1, Table 2 or Table 3.

Embodiment 2

The method of embodiment 1, wherein said high throughput method comprises nanopore sequencing.

Embodiment 3

The method of embodiment 1 or 2, wherein said nucleic acid sample comprises RNA.

Embodiment 4

The method of embodiment 3, wherein said RNA comprises mRNA.

Embodiment 5

The method of embodiment 1 or 2, wherein said nucleic acid sample comprises DNA.

Embodiment 6

The method of embodiment 5, wherein said DNA comprises cDNA, genomic DNA, sheared DNA, cell free DNA, fragmented DNA, or PCR amplified products produced therefrom, or any combination thereof.

Embodiment 7

The method of embodiment 5, wherein said DNA comprises DNA from an endometriosis lesion or peritoneal fluid.

Embodiment 8

The method of any one of embodiments 1-7, wherein said one or more genetic variants comprise a genetic variant defining a minor allele.

Embodiment 9

The method of any one of embodiments 1-7, wherein said one or more genetic variants comprise at least about: 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 500, or more genetic variants defining minor alleles.

Embodiment 10

The method of any one of embodiments 1-9, wherein detection of said one or more genetic variants has an odds ratio (OR) for endometriosis of at least about: 1.5, 2, 5, 10, 20, 50, 100, or more.

Embodiment 11

The method of any one of embodiments 1-10, wherein said one or more genetic variants comprise a synonymous mutation, a non-synonymous mutation, a stop-gain mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof.

Embodiment 12

The method of any one of embodiments 1-11, wherein said one or more genetic variants comprise a protein damaging mutation.

Embodiment 13

The method of any one of embodiments 12, wherein said one or more genetic variants further comprise a protein damaging or loss of function variant in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof.

Embodiment 14

The method of any one of embodiments 1-12, wherein said one or more genetic variants are comprised in GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR or a combination thereof.

Embodiment 15

The method of any one of embodiments 1-13, further comprising detecting one or more additional variants defining a minor allele listed in Table 4.

Embodiment 16

The method of any one of embodiment 1-15, wherein said one or more genetic variants are identified or weighted based on a predictive mathematical or computer programmed algorithm.

Embodiment 17

The method of any one of embodiments 1-16, wherein said one or more genetic variants are identified based on reference to a database.

Embodiment 18

The method of any one of embodiments 1-17, further comprising identifying said subject as having endometriosis or being at risk of developing endometriosis.

Embodiment 19

The method of embodiment 18, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 20

The method of any one of embodiments 18-19, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 21

The method of any one of embodiments 18-20, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

Embodiment 22

The method of any one of embodiments 18-21, wherein said subject is identified as having endometriosis.

Embodiment 23

The method of embodiment 22, wherein said subject is asymptomatic for endometriosis.

Embodiment 24

The method of embodiment 22, wherein said subject is symptomatic for endometriosis.

Embodiment 25

The method of any one of embodiments 18-21, wherein said subject is identified as being at risk of developing endometriosis.

Embodiment 26

The method of any one of embodiments 1-25, further comprising administering a therapeutic to said subject.

Embodiment 27

The method of embodiment 26, wherein said therapeutic comprises hormonal therapy, an advanced reproductive technology therapy, a pain managing medication, or any combination thereof.

Embodiment 28

The method of embodiment 26, wherein said therapeutic comprises hormonal contraceptives, gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn-RH) antagonists, progestin, danazol, or any combination thereof.

Embodiment 29

The method of any one of embodiments 26-28, wherein said therapeutic comprises a pain medication.

Embodiment 30

The method of embodiment 29, wherein said pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof.

Embodiment 31

The method of any one of embodiments 1-26, wherein said one or more genetic variants are listed in Table 1.

Embodiment 32

The method of any one of embodiments 1-26, wherein said one or more genetic variants are listed in Table 2.

Embodiment 33

The method of any one of embodiments 1-26, wherein said one or more genetic variants are listed in Table 3.

Embodiment 34

The method of any one of embodiments 1-33, further comprising identifying said subject as having endometriosis-associated infertility or being at risk of developing endometriosis-associated infertility.

Embodiment 35

The method of embodiment 34, further comprising administering assisted reproductive technology therapy to said subject.

Embodiment 36

The method of embodiment 35, wherein said assisted reproductive technology therapy comprises in vitro fertilization, gamete intrafallopian transfer, or any combination thereof.

Embodiment 37

The method of embodiment 34, further comprising administering intrauterine insemination or ovulation induction.

Embodiment 38

The method of any one of embodiments 1-37, wherein said subject is a mammal.

Embodiment 39

The method of embodiment 38, wherein said mammal is a human.

Embodiment 40

The method of any one of embodiments 2-39, wherein said nanopore sequencing is performed with a biological nanopore, a solid state nanopore, or a hybrid nanopore.

Embodiment 41

The method of any one of embodiments 1-40, wherein said one or more genetic variants further comprise a mutation in SEPT10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof.

Embodiment 42

The method of embodiment 41, wherein said one or more genetic variants comprise a mutation in SEPT10 and wherein said mutation comprises a missense mutation.

Embodiment 43

The method of embodiment 41, wherein said one or more genetic variants comprise a mutation in TNFRSF6B and wherein said mutation comprises a homozygous or hemizygous mutation.

Embodiment 44

The method of embodiment 41, wherein said one or more genetic variants comprise a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion.

Embodiment 45

The method of any one of embodiments 1-44, wherein the one or more variants are identified based on a predictive computer algorithm.

Embodiment 46

The method of embodiment 45, wherein said predictive computer algorithm is Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, or MetaLR.

Embodiment 47

The method of any one of embodiments 1-46, further comprising administering a hormonal therapy to said subject.

Embodiment 48

The method of embodiment 47, wherein the hormonal therapy comprises administration of hormonal contraceptives, gonadotropin-releasing hormone (GnRH) agonists, gonadotropin-releasing hormone (GnRH) antagonists, progestin, danazol, or any combination thereof.

Embodiment 49

The method of any one of embodiments 1-46, further comprising administering to the subject an assisted reproductive therapy.

Embodiment 50

The method of embodiment 49, wherein the assisted reproductive therapy comprises in vitro fertilization, intrauterine insemination, ovulation induction, gamete intrafallopian transfer, or any combination thereof.

Embodiment 51

The method of any one of embodiments 1-46, further comprising administering to the subject a pain medication.

Embodiment 52

The method of embodiment 51, wherein the pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof.

Embodiment 53

The method of any one of embodiments 1-46, further comprising administering a therapeutic to the subject.

Embodiment 54

The method of embodiment 53, wherein the therapeutic comprises a regenerative therapy, a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof.

Embodiment 55

The method of embodiment 53, wherein the therapeutic comprises a non-steroidal anti-inflammatory, a hormone treatment, a dietary supplement, a cannabis-derived therapeutic or any combination thereof.

Embodiment 56

The method of embodiment 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises an at least partially hemp-derived therapeutic, an at least partially cannabis-derived therapeutic, a cannabidiol (CBD) oil derived therapeutic, or any combination thereof.

Embodiment 57

The method of embodiment 53, wherein the therapeutic comprises the medical procedure, and wherein the medical procedure comprises a laparoscopy, a laser ablation procedure, a hysterectomy or any combination thereof.

Embodiment 58

The method of embodiment 53, wherein the therapeutic comprises the regenerative therapy, and wherein the regenerative therapy comprises a stem cell, a cord blood cell, a Wharton's jelly, an umbilical cord tissue, a tissue, or any combination thereof.

Embodiment 59

The method of embodiment 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises cannabis, cannabidiol oil, hemp, or any combination thereof.

Embodiment 60

The method of embodiment 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition is formulated in a unit dose.

Embodiment 61

The method of embodiment 53, wherein the therapeutic comprises hormonal therapy, an advanced reproductive therapy, a pain managing medication, or any combination thereof.

Embodiment 62

The method of embodiment 53, wherein the therapeutic comprises a hormonal contraceptive, gonadotropin-releasing hormone (GnRH) agonist, gonadotropin-releasing hormone (GnRH) antagonist, progestin, danazol, or any combination thereof.

Embodiment 63

The method of any one of embodiments 1-62, wherein the subject is asymptomatic for endometriosis.

Embodiment 64

A kit comprising: one or more probes for detecting one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof in a sample.

Embodiment 65

The kit of embodiment 64, further comprising a control sample.

Embodiment 66

The kit of embodiment 64, wherein the control sample comprises one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof.

Embodiment 67

The kit of any one of embodiments 64-66, wherein the one or more probes comprise a hybridization probe or amplification primer.

Embodiment 68

The kit of any one of embodiments 64-67, wherein the one or more probes is configured to associate with a solid support.

Embodiment 69

The kit of any one of embodiments 64-68, wherein the kit further comprises instructions for use and wherein the instructions for use comprise high stringent hybridization conditions.

Embodiment 70

The kit of any one of embodiments 64-69, wherein the one or more probes is configured to hybridize to a target region of a nucleic acid of the sample, wherein the target region comprises one or more genetic variants.

Embodiment 71

A system comprising: (a) a computer processor configured to receive sequencing data obtained from assaying a sample, wherein the computer processor is configured to identify a presence or an absence of one or more genetic variants of Table 1, Table 2, Table 3 or any combination thereof in the sample, and (b) a graphical user interface configured to display a report comprising the identification of the presence or the absence of the one or more genetic variants in the sample.

Embodiment 72

The system of embodiment 71, wherein the computer processor comprises a trained algorithm.

Embodiment 73

The system of embodiment 71 or 72, wherein the computer processor communicates a result.

Embodiment 74

The system of embodiment 73, wherein the result comprises an identification of the presence or the absence of one or more genetic variants in the sample.

Embodiment 75

A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting a genetic variant in said nucleic acid sample, wherein said genetic variant comprises a mutation in SEPT10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof.

Embodiment 76

The method of embodiment 75, wherein said genetic variant is a mutation in SEPT10 and wherein said mutation comprises a missense mutation.

Embodiment 77

The method of embodiment 75, wherein said genetic variant is a mutation in TNFRSF6B and wherein said mutation comprises a homozygous or hemizygous mutation.

Embodiment 78

The method of embodiment 75, wherein said genetic variant is a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion.

Embodiment 79

The method of embodiment 75, wherein said high throughput method comprises nanopore sequencing.

EXAMPLES

Example 1. Low-Frequency, Damaging Mutations in Hundreds of Genes are Risk Factors for Endometriosis

This study performed exome-wide association analysis for rare low frequency mutations in the women with endometriosis. Rare exome variants associated with endometriosis were searched using an exome genotyping array and confirmatory whole exome sequencing (WES).

Consent and Medical Review

All subjects and controls were provided written informed consent in accordance with study protocols approved by Quorum Review IRB (Seattle, Wash. 98101). Trained OB/GYN clinicians performed the medical record review and clinical assessment of each patient.

Methods

Illumina Exome Human BeadChip. 1518 Caucasian patients with surgically confirmed endometriosis were tested for more than 200,000 rare non-synonymous variants (minor allele frequency <0.005). Allele frequencies were compared to the population datasets (genotyping dataset UK Michigan (n=50,000) and publicly available sequencing dataset Exac (n=33,000).

Affymetrix Axiom Custom Chip. 1888 Caucasian patients with surgically confirmed endometriosis were tested for more than 700,000 variants. Allele frequencies were compared to the population sequencing dataset Exac (n=33,000). Replication was performed on 530 endometriosis subjects with whole exome sequencing data. Association testing was performed using Fisher's exact test. Nominal threshold was selected for significance (p<0.05). Panther software was used to test gene ontologies. A predictive score (E) was estimated for each subject as follows: E=Σ log(L95ORj)*Cj, in which C is a count of risk allele, L95OR is a lower limit of 95% CI of an odds ratio, and j is 1, 2, 3 . . . n, wherein n is the number of the associated variants.

Results

775 rare variants associated with endometriosis were identified, 561 of which were identified using Illumina Exome Beadchip, and 214 of which were identified using Affymetrix Axiom Custom Chip. FIG. 1A-1B to FIG. 3 illustrate the results. Multiple low-frequency coding variants can be important in the genetic architecture of endometriosis. The relative risk of having endometriosis is significantly higher in women with multiple damaging variants, suggesting that they may serve as useful predictive or diagnostic markers. Genes involved with Wnt, cadherin, integrin, and inflammation medicated by cytokine signaling pathways are enriched, but trends did not reach significance.

Example 2. Genetic Variation Underlying the Clinical Heterogeneity of Endometriosis

The study investigated whether two of the typical symptoms—pain and infertility may be linked to distinct genetic factors. A pool of 2818 non-synonymous SNP markers were selected to classify markers associated with pain or infertility patients. In one group, cases were included that reported pain as their primary symptom but not infertility (n=727), and in the other group, cases were included with infertility as their primary symptom with only minimal or no pain (n=138). SNPs were then evaluated for significant variation between the two groups.

Methods

Genotyping. The samples were genotyped on a custom designed microarray using the Affymetrix Axiom platform per the manufacturer's instructions.

Statistical Analysis. Differences in allele frequencies between the two cohorts were tested for each SNP by a 1-degree-of-freedom Corchran-Armitage Trend test.

Ethnicity. Subjects were confirmed Caucasian ethnicity using principal component analysis.

Population Controls. The marker frequencies were compared to population control dataset of European Ethnicity (n=33,000; ExAc Database) to associate the marker to the respective group.

Consent and Medical Review

All subjects were provided written informed consent in accordance with study protocols approved by Quorum Review IRB (Seattle, Wash. 98101). Trained OB/GYN clinicians performed the medical record review and clinical assessment of each patient. Inclusion criteria in the endometriosis case population in the study were surgically confirmed diagnosis of endometriosis.

Results

The analysis identified nine SNP variants with differential prevalence between pelvic pain patients and infertility patients as shown in Table 5.

	AA	Allele Frequency	CPP vs. INF
SNP	Gene	Chr	Pos	change	ExAC	GPP	INF	Ptrend	OR
Genes associated with chronic pain
rs172562	TBX18	6	85,473,758	G48R	0.5706	0.4805	0.5766	0.0024	1.47
rs12339210	WHRN/	9	117,170,241	P562A	0.1636	0.1007	0.1606	0.0040	1.69
	DFNB31
rs35471617	COL21A1	6	56,033,094	T343M	0.1274	0.0639	0.1159	0.0021	1.92
rs72899872	LPR1B	2	141,232,800	A3178T	0.0127	0	0.0109	0.0001	∞
Genes associated with infertility
rs8139422	CRELD2	22	50,315,363	D182E	0.0313	0.0282	0.0616	0.0040	2.27
rs78214713	OR51Q1	11	5,444,040	L204F	0.0066	0.0089	0.029	0.0259	3.33
rs7597367	SCLY	2	238,973,062	K60E	0.0006	0	0.0073	0.0011	∞
rs35880972	BIRC8	19	53,793,162	A156T	0.0004	0	0.0072	0.0012	∞
rs34505126	BMP3	4	81,967,240	T222M	0.0006	0	0.0072	0.0012	∞

Table 5 summarizes the results from a comparison of endometriosis associated variants with significantly different allele frequencies between patients with pelvic pain or infertility. ExAc can refer to frequencies reported by the ExAc consortium. CPP can refer to chronic pelvic pain and INF to infertility. Italic front indicates frequencies deviant from the general population.

The analysis identified five genes (CRELD2, OR51Q1, SCLY, BIRC8, BMP3) associated with infertility and four genes (TBX18, WHRN, COL21A1, LRP1B) associated with chronic pain. There was a sufficient power (>0.8) to detect markers with OR greater than 1.5 at significance level of 0.05. A review of the function of the genes identified can implicate several of the genes in both the pain and infertility pathways. Both WHRN and TBX18 which show differential allele frequencies in patients with pelvic pain have been shown to be linked to pain-pathways. Mutations in WHRN have been linked to deafness and mechano- and thermo-sensitive deficiencies and can stabilize the paranodal region and axonal cytoskeleton in myelinated axons. TBX18 is an important development regulator of the pericardium, prostate, nephrons, urogenital tubes, and seminiferous tubules and mutations in TBX18 have been linked to pain in the chest, back, and flank. Conversely, CRELD2 which show differential allele frequencies in infertility patients is linked with fertility. CRELD2 is expressed in Oviductal epithelial cells in a manner that is very strongly correlated with the menstrual cycle and suggestive of an important reproductive role.

Pain and infertility can be two common but distinct clinical symptoms of endometriosis. In the present study, 9 non-synonymous variants were identified from a broad group of endometriosis associated variants that show distinct association with only one of the two symptoms and thus are suggestive of genetic classification of clinical subgroups of endometriosis.

Example 3. Novel High-Risk Damaging Mutations Discovered in Familial Endometriosis

Whole exome sequencing (WES) was used in endometriosis families to determine if inherited, rare, high-risk protein coding variants contribute to endometriosis. Endometriosis is a complex disease with underlying genetic and environmental factors. Array-based genotyping platforms are well suited for GWA studies detecting association with common variants (minor allele frequencies >3-5%), whereas sequencing is required to detect rare and low-frequency protein coding variants. Subjects with familial endometriosis tend to carry a higher burden of genetic variants; families can be less likely to have potentially confounding (population stratification) effects. Studying genetic variants located on the same DNA strand (haplotypes) can help resolve the inheritance pattern of a disease variant by determining if two individuals who carry the same genetic variant have inherited the variant via shared recent ancestry (same haplotype) or whether their variants are derived from two independent mutation events (different haplotypes).

Methods

WES was performed on 489 women with familial endometriosis and 530 unrelated women (confirmed with identity-by-descent test) with endometriosis. Wes was also performed using Ion Proton Instrument (FIG. 4) and AmpliSeq Exome Capture kit. All missense and protein truncating variants with a MAF<1% in ExAc database (Broad Institute) were considered for downstream analysis. Variant frequencies were compared with population frequency in ExAc database (n=33,000) using Fisher's exact test (exac. broadinstitute.org). Several software packages were used to predict whether the identified mutation would damage the encoded protein.

Consent and Medical Review

All subjects were provided written informed consent in accordance with study protocols approved by Quorum Review IRB (Seattle, Wash. 98101). Inclusion criteria were surgically confirmed diagnosis.

Results

This study identified 4 protein damaging variants significantly more prevalent in familial endometriosis. The 4 high-risk variants also pass genome-wide significance as shown in Table 6 below. Association was verified for all but the BRD9 variant in the cohort of unrelated endometriosis patient.

TABLE 6
Four genes with low-frequency damaging mutations showing association to endometriosis.
	Index mutation	Gene burden
Gene	AAchange	EndoFrq	ExacFrq	P	OR	EndoFrq	ExacFrq	P	OR
LONP1	splice	0.0028	Not	4.2 × 10−19	Inf	0.0302	0.0199	2.6 × 10−2	1.5	[1-2]
			seen
IGF2	Q33X	0.0048	0.0009	3.0 × 10−10	15	[8-27]	0.0085	0.0014	3.0 × 10−5	6	[3-12]
BRD9	K39R	0.0009	0.0017	5.6 × 10−9	10	[5-21]	0.0057	0.0101	2.1 × 10−1	0.6	[0.3-1.3]
SNAP91	T555A	0.0106	0.0050	1.1 × 10−8	5	[3-8]	0.0179	0.0045	1.3 × 10−6	4	[2-6]

LONP1 (Lon protease) is a nuclear encoded protease in the mitochondria responsible for the degradation of misfolded proteins. LONP1 is expressed in endometrium and endometrial cancer, and affects endothelial mesenchymal transition in a dose dependent manner. Using a Genealogy database (GenDB) a shared ancestor ˜13 generations ago was identified. All affected individuals shown with LONP1 variant in FIG. 5 share identical haplotype of ˜140 kb which is concordant with a single shared ancestor 11-15 generations in the past.

IGF2 (Insulin-like growth factor 2) has previously been implicated in endometriosis in Korean women. The IGF axis has been implicated in growth regulation of endometriosis. In blood, IGF2 is an imprinted gene expressed only from the paternal haplotype.

SNAP91 (Synaptosome Associated Protein 91) and BRD9 (Bromodomain Containing 9) are novel endometriosis candidates but little is known about their function.

This study identified low-frequency damaging protein mutations segregating in families with endometriosis. IGF2 is the second implicated gene identified associated with endometriosis after NLRP2. Only 50 imprinted genes are known in humans to date suggesting imprinting plays a role in endometriosis. LONP1 and IGF2 regulate EMT in the pathogenesis of endometriosis.

Example 4. CCDC168 and MUC12 Show Recessive Effects in Women with Endometriosis

Compound heterozygosity help identify genes involved in endometriosis. Whole Exome Sequencing (WES) was used on samples from 1,385 participants.

Samples

1019 Endometriosis samples were sequenced, 530 of which were for discovery, 301 of which were for replication, and 188 of which were related (2^nd cousin or closer). 366 control samples were sequenced.

Variant and Gene selection

Protein-altering variants in discovery w frequency <1% in ExAC. 3039 genes were found individuals with 2+ variants per gene in the discovery set and thus can possibly be recessive genes. FIG. 6 illustrates mutation patterns cis/trans/haplotypes. Excess burden analysis of samples with 2+ protein-altering variants. Discovery (530 Endo vs 366 Ctl)− two genes with excess burden, P_Fisher<0.001. Replication (301 Endo vs 366 Ctl)− both genes replicate, P_Fisher<0.05.

Results

CCDC168 and MUC12 show significant excess variant count in endometriosis. Sample counts with rare protein-altering variants (ExAC_freq<1%)

TABLE 7
Variant count of CCDC168
	95 Unique variants	2+	0-1
	Cases	31	988
	Controls	0	366
	gnomAD (0.05)	1	365

TABLE 8
Variant count of MUC12
	82 Unique variants	2+	0-1
	Cases	47	970
	Controls	1	365
	gnomAD (0.14)	7	359

The variant counts of 2+ include all homozygotes, hemizygotes, and compound heterozygotes (cis and trans). Both genes show significant excess in endometriosis samples with 2+ hits also when compared with gnomAD.

The two novel genes, CCDC168 and MUC12, have large recessive effects in endometriosis and can be biologically relevant in endometriosis. 7.6% of endometriosis patients can have compound heterozygote mutations with 4-30 fold excess compared with control populations.

CCDC168 is coiled-coil domain containing 168. CCDC168 can be differentially expressed in malignancies. Antibody staining can show prominent staining in various epithelial tissues. In some instances, CCDC168 is only present in placental animals (those with endometrium).

MUC12 is a transmembrane mucin expressed across many epithelial tissues including colon, pancreas, prostate or uterus. In some instances, transmembrane mucins are single-stranded proteins undergo proteolytic cleavage splitting TM and EC domains, lubricate epithelial surfaces, bind ligands, regulate epithelial wound healing, and/or extracellular domain detach with excess force (intracellular signaling and EMT). In some instances, a transmembrane mucin disclosed herein is MUC1, MUC4, MUC12, or MUC16. The extra cellular domain of MUC16 can be cancer antigen 125 (CA125), an important marker of ovarian cancer and endometriosis.

Example 5. Rare Synonymous Mutations Show Strong Association with Endometriosis

The study is to determine if rare synonymous variants might contribute to the genetic risk for developing endometriosis. Synonymous and non-synonymous DNA variants can occur within the protein-coding part of a gene. Synonymous variants do not affect the amino-acid sequence, and non-synonymous variants do affect the amino-acid sequence, due to the redundancy in the genetic code. GWAS intergenic SNP variants may be determined from eQTL fine mapping, and rare non-synonymous variants may be determined from Whole Exome Sequencing.

Methods

Whole exome sequencing was performed on 1,077 study participants with surgically diagnosed endometriosis. Saliva DNA underwent AmpliSeq sequencing on an Ion Proton, and sequence was assembled using the Torrent software. Variant frequencies were compared to frequencies in gnomAD, which was used as reference for population-wide variant frequencies. Synonymous variants with a minor allele frequency <0.01 in the general population were considered. Fisher's Exact test was used to calculate association statistics. PANTHER database was used for GO (Gene Ontology) term enrichment analysis.

Results

114,877 synonymous rare variants were identified among patients. 648 synonymous variants passed the nominal significance threshold (p<0.05) across 617 genes. Table 9 shows five variants strongly associated with endometriosis that pass the genome-wide significance threshold of p≤5×10⁻⁸.

TABLE 9
Five strongly associated synonymous variants
Gene	Chr	Position	P	OR	Nucl change	Amino Acid
KRTAP5-1	11	1,606,402	2.0 × 10−11	43	C78T	S26S
GPR137	11	64,051,889	6.7 × 10−15	49	G51A	G17G
UBC	12	125,398,297	1.5 × 10−33	94	T21C	T7T
ADAMTS7	15	79,058,944	2.5 × 10−11	11	T3309A	A1103A
SYNE1	6	152,457,795	6.7 × 10−8	5	G25617A	E8539E

17 genes have 2-or-more rare synonymous disease associated variants were found with only one expected by chance (p<0.001): ABCC5, ANK3, ATP8B4, CCDC147, CELSR1, DNAH3, EML6, HERC2, ITGA2, KIF23, LAMA5, PKD1, SLC22A20, SSPO, TENM2, TUBGCP2, VPS18. GO-term analysis show significant enrichment of a single GO term: “cytoskeletal structure and regulation” (OR=13.4). Rare intronic splice-junction variants were considered among the 17 genes, and 5 variants in CCDC147, LAMA5, and SSPO may affect the risk-burden.

This is the first time that rare synonymous variants may have been implicated in endometriosis. The genes may carry these mutations that are enriched for cytoskeletal function. Go-term and functional analysis implicate cytoskeletal regulation in the genetic predisposition of endometriosis. There variants may prove useful in developing a non-invasive test for endometriosis.

Example 6. Large Effect Mutations in Endometriosis Genes Implicated by GWAS

Genome-wide association studies (GWAS) implicate several chromosomal regions as genetic risk factors for endometriosis. These regions have been “tagged” by polymorphic markers located between genes or in non-coding introns. Sequenced were the exons of 16 genes in GWAS regions to search for causative mutations, i.e., to find gene mutations responsible for the association observed in 16 genes implicated by endometriosis GWAS.

Methods

AmpliSeq sequencing on Ion Protons was conducted on DNA samples from 1,019 women with confirmed endometriosis. After sequence assembly using Torrent software, variant annotation was performed using ANNOVAR (hg19 reference). Frequencies of coding variants were compared against a large reference dataset (sequence data from 63,369 non-Finnish Europeans in gnomAD). Variants were found using Torrent Variant Caller (UCSC hg19). Association statistics were calculated using Fisher's Exact test; linkage disequilibrium statistics were calculated using LDlink. Cases: n=1,019 European women with confirmed endometriosis. Controls: n=63,369 non-Finnish Europeans in gnomAD).

Results

571 variants were detected; 333 of these alter an amino acid in the encoded protein and 234 low-frequency (MAF<1%), missense mutations are predicted to be pathogenic (in-silico). Likely pathologic variants are uncommon in the reference data (which contains women with endometriosis and males carrying risk factors); but the identified variants were often seen in multiple endometriosis patients. The excess of pathogenic mutations in cases was striking (p<10⁻¹⁶). 4 mutations (see Table 10) have high odds ratios for endometriosis with p values well below a multiple testing threshold (p≤9×10⁻⁵). Mutations predicted to shorten the encoded protein (loss of function) were also detected (2 splicing changes, and 7 “stop” mutations). Stop mutations (seen in five genes: GREB1, NFE2L3, FN1, SYNE1 and VEZT) were more prevalent in the endometriosis cohort compared to the population data (p=1.7×10⁻¹³). There is no measureable linkage disequilibrium between any of the new variants and tagging GWAS markers. FIG. 7 to FIG. 9 further illustrate the results.

TABLE 10
Mutations with p values below multiple correction threshold. Inf
means that the variant was not observed in the control cohort.
			Endo-
	Protein	Control	metriosis		Odds Ratio
Gene	change	Frequency	Frequency	p(fisher)	[L95-U05]
FN1	p.V527M	Not seen	0.00147	4.03E−06	Inf.
NFE2L3	p.I233V	Not seen	0.00147	4.03E−06	Inf.
SYNE1	p.E8539E	0.00206	0.00785	1.11E−05	3.84
VEZT	p.P712S	0.00005	0.00196	1.23E−05	41.50

This is the first comprehensive study of coding mutations in all 16 GWAS candidate genes. Coding variants may not explain the association observed in GWAS studies, thus regulatory mutations outside of the coding regions are likely to be involved. The mutations having large effects confirm an important role for these genes in the pathogenesis of endometriosis.

Example 7. Detailed Methods for Detection of Low Frequency Variants

Medical Review.

The inclusion criteria in the endometriosis case population in the present study were surgically confirmed diagnosis of endometriosis with laparoscopy being the preferred method. Trained OB/GYN clinicians performed the medical record review and clinical assessment of each individual patient. Patients were considered to be affected if they had biopsy-proven lesions or if operative reports revealed unambiguous gross lesions. Patients were further categorized by severity, clinical history of pelvic pain, infertility, dyspareunia or dysmenorrhea and family history. Patients were grouped into one of three classes of severity: mild, moderate or severe, following the general guidelines set forth by ASRM. This analysis compared cases with 100% prevalence of endometriosis to controls with the population prevalence of endometriosis (5-10%).

DNA Extraction.

Saliva samples were collected using the Oragene 300 saliva collection kit (DNA Genotek; Ottawa, Ontario, Canada) and DNA was extracted using an automated extraction instrument, AutoPure LS (Qiagen; Valencia, Calif.), and manufacturer's reagents and protocols. DNA quality was evaluated by calculation absorbance ratio OD260/OD280, and DNA quantification was measured using PicoGreenH (Life Technologies; Grand Island, N.Y.).

Microarray Genotyping.

The discovery set of 2019 endometriosis cases and 25476 population controls were genotyped using the Illumina Human OmniExpress Chip (Illumina; San Diego, Calif.) according to protocols provided by the manufacture. An additional 905 endometriosis cases were genotyped on a custom designed microarray using the Affymetrix GeneTitan platform according to the manufacturer's instructions.

Sample Quality Control.

Samples were excluded from the analysis if they missed any of the following quality thresholds:

• • a) Evidence of familial relationship closer that 3rd-degree (pi-hat>0.2) using genome-wide Identity-By-State (IBS) estimation implemented in PLINK
  • b) Samples with missing genotypes >0.02
  • c) Samples with non-European admixture >0.05 as determined by ADMIXTURE

SNP Quality Control.

SNPS were excluded from the analysis if they missed any of the following quality thresholds:

• • a) SNPs from copy number variant regions or regions with adjacent SNPs
  • b) SNPs failing Hardy-Weinberg Equilibrium (HWE) P<=10⁻³
  • c) SNPs with minor allele frequency (MAF)<=0.01 in the control population
  • d) SNP call rate <=98%

Admixture.

ADMIXTURE (ver. 1.22) was used to estimate the individual ancestry proportion. The software estimates the relative admixture proportions of a given number of a priori defined ancestral groups contributing to the genome of each individual. The POPRES dataset (Nelson M R et al. 2008) was used as a reference group to create a supervised set of 9 ancestral clusters. Seven of them belong to the European subgroups along with African and Asian groups. Since POPRES dataset utilized Affymetrix 5.0 chip, 105,079 autosomal SNPs that overlapped with the Illumina OmniExpress dataset were used. Among the 105,079 SNPs, a subset of 33,067 SNPs was selected that showed greater genetic variation (absolute difference in frequency) among the 9 reference groups. The pair-wise autosomal genetic distance determined by Fixation Index (FST) using 33,067 SNPs was calculated for the 9 reference groups as listed in POPRES dataset. Subsequently, a conditional test was used to estimate the admixture proportions in the unknown samples as described by Alexander et al. (2009).

Principal Component Analysis (PCA).

PCA was applied to account for population stratification among the European subgroups. The previously identified 33,067 SNPs were selected to infer the axes of variation using EIGENSTRAT. Only the top 10 eigenvectors were analyzed. Most of the variance among the European populations was observed in the first and second eigenvector. The first eigenvector accounts for the east-west European geographical variation while the second accounts for the north-south component. Only the top 10 eigenvectors showed population differences using Anova statistics (p<0.01). The PCA adjusted Armitrage trend P-values were calculated using the top 10 eigenvectors as covariates.

Association Analysis.

After the quality of all data was confirmed for accuracy, genetic association was determined using the whole-genome association analysis toolset, PLINK (ver. 1.07). Differences in allele frequencies between endometriosis patients and population controls were tested for each SNP by a 1 degrees of freedom Cochran-Armitrage Trend test. The allelic odds ratios were calculated with a confidence interval of 95%. SNPs that passed the quality control parameters were prioritized using the PCA adjusted cochran-Armitrage trend test P-values. The combined/metaanalysis of different datasets was performed using Cochran-Mantel-Hanszel method as well as using Cochran-Armitrage Trend test. Breslow Day test was used to determine between-cluster heterogeneity in the odds ratio for the disease/SNP association.

Software Used.

PLINK (version 1.07). R (version 2.15.0). EIGENSTRAT (version 3.0).

Example 8. Detailed Methods for Gene Sequencing and Detection of Low-Frequency Damaging Variants

DNA Extraction and Genotyping.

DNA used in the present study was extracted from blood or saliva using standard extraction methods. Genotyping was performed using the Illumina HumanExome (Illumina, San Diego, Calif.) according to protocols provided by the manufactures.

Sample and SNP Quality Control

The discovery set of 1518 cases were genotyped using the Illumina Human Exome Chip (Illumina; San Diego, Calif.) per protocols provided by the manufacture.

Samples were excluded from the analysis if they missed any of the following quality thresholds:

• • a) Evidence of familial relationship closer that 3rd-degree ({circumflex over (π)}>0.2) using genome-wide Identity-By-State (IBS) estimation implemented in PLINK.
  • b) Samples with missing genotypes >0.02
  • c) Samples with non-European admixture >0.05 as determined by ADMIXTURE

SNPS were excluded from the analysis if they missed any of the following quality thresholds:

• • a) SNPs with Illumina GenTrain Score <0.65
  • b) SNPs from copy number variant regions or regions with adjacent SNPs
  • c) SNP call rate ≤98%

Exome Sequencing and Variant Discovery

Whole exome sequencing (WES) was performed on 2400 endometriosis cohort using Ion Proton Instrument as per the manufacturer's protocol (Life Technologies, Carlsbad Calif.) using their AmpliSeq Exome Capture Kit. Sequence alignment and variant calling was performed against the reference human genome (UCSC hg19 version). The variant discovery was performed using Life Technologies TMAP algorithm with their default parameter settings, and Life Technologies Torrent Variant Caller was used to discover variants. The variants identified from the Torrent Variant Caller were taken further for downstream analysis. The variants included were single nucleotide variants, short insertions, or deletions. Variant annotation was performed using ANNOVAR. The coding variants were classified as missense, frameshift, splicing, stop-gain, or stop-loss. Variants were considered “loss-of-function” if they caused a stop-gain, splicing, or frame-shift insertion or deletion. Prediction of protein function was evaluated in silico using seven different algorithms (Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, and MetaLR. Missense variants were deemed “damaging missense” if they were predicted damaging by at least one of the seven algorithms tested. The genes that harbor these variants were also checked against the published “FLAGS” gene list (Shyr C et al. 2014) to understand whether the gene is frequently mutated in humans.

Low Frequency Variants

Variants that pass the population control frequency (gnomAD) of MAF<1% were called “low frequency variants”. These variants were analyzed to test for association using Fisher's Exact Test. The low frequency variants were prioritized based on their Fisher's p value.

Gene Burden

The genetic burden was calculated for each gene by collapsing/combining all low frequency variants identified through WES. Fisher's Exact Test was used to determine excess gene burden in endometriosis subjects compared to the control population counts as observed in gnomAD database by generating 2×2 table per gene for the number of reference and alternative alleles. The genes were then prioritized based on their Fisher's p value.

Example 9. Whole Exome Sequencing Identifies Markers of Endometriosis

Twin and family studies show that heritability for endometriosis may be high, yet the GWAS markers and copy number variants identified explain about 5% of the heritability. Multigenerational pedigrees can be used to identify variants/genes with large effects in complex diseases. A large endometriosis family spanning 19 generations with 218 women with surgically confirmed disease was used for this study. For endometriosis, one cannot assume that all distant relatives share a single causative mutation. However, segregation analyses suggest that autosomal major gene effects may be likely. Referring to FIG. 12, whole exome sequencing (WES) was performed on 137 women with surgically confirmed endometriosis having a common ancestor born in 1608. The WES was utilized to search for pathogenic mutations. All coding variants were evaluated. Variants may be deemed damaging if they were predicted to be damaging “in-silico” by at least one algorithm of Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, or MetaLR. The excess variant burden in this family was compared against population controls (e.g. exome sequencing data for the non-Finnish European cohort in the gnomAD database, wherein n=55,860).

A damaging missense variant (p.T166I) in SEPT10 gene seen in about 0.18% of controls was seen in a 20 fold excess (3.6%) in the large endometriosis family (p=1.98×10⁻¹⁰; Odds Ratio (OR)=20.6 [10.8=39.30]. SEPTIN10 is a cytoskeletal protein that may have GTP-binding and GTPase activity. Referring to FIG. 13, septins may polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules.

Referring to FIG. 14, a TNFRSF6B haplotype (also called DcR3) which spans 41 kb was present in 76 of the 137 subjects with surgically confirmed endometriosis (p=1.7×10⁻⁸; Odds Ratio (OR)=2.11); 21 of the affected women were homozygous or hemizygous. These results suggest mutations in one or more genes—TNFRSF6B and SEPT10—may be diagnostic for predicting a risk of developing or confirming a presence of endometriosis.

Example 10. Whole Exome Sequencing Identifies Markers of Endometriosis

Endometriosis affects from about 6% to about 10% of women during their reproductive years with symptoms including pelvic pain, dyspareunia, dysmenorrhea, infertility, or any combination thereof. Twin and family studies show that heritability for endometriosis may be high; yet common genetic variations identified by genome-wide association studies only explain about 5% of the heritability. It is possible that rare and recent familial mutations, not detectable by GWAS, may be responsible for part of the missing heritability. Next generation sequencing gives the opportunity to look for less-common variants with large effects. In this study, we used whole exome sequencing (WES) to identify inherited deletion variants in a three generation family of seven affected women with surgically confirmed endometriosis.

Exome sequencing was performed using the AmpliSeq technology on Ion Proton platform (Thermo Fisher, Inc) according to manufacturers instructions. Variants were determined using Ion Proton protocol and confirmed using the GATK (Genome Analysis Toolkit) pipeline. Segmental deletions were identified by observing three-or-more homozygous neighboring variants in the matriarch that failed to segregate in a Mendellan manner in her daughters/grand-daughters.

A three-generation family with seven affected members is shown in FIG. 15 together with notable symptoms tabulated to the right of the pedigree.

Case 1 was the first individual in the family to be diagnosed with endometriosis and underwent surgical hysterectomy at age 32 due to stage IV bilateral ovarian endometriosis. Her mother (not shown in the pedigree) had four children with no gynecological problems. However, her three daughters (cases 2-4) and three grand-daughters (cases 5-7) all have been surgically diagnosed with endometriosis. In addition to endometriosis, case 1 has been diagnosed with 14 other morbidities including Crohn's disease, interstitial cystitis, bronchial asthma, cardiovascular diseases, lupus erythematosus and multiple sclerosis, all of which have been positively associated with endometriosis.

Referring to FIG. 16, we identified approximately 20,000 exonic variants in each of the seven individuals, and almost 34,000 variants combined across the pedigree, which is in line with expectations. IBD and segregation analysis confirmed all individual relationships and the overall pedigree structure. We identified two hemizygous deletions segregating in this three-generation family. A deletion was found in UGT2B28 (UDP Glucuronosyltransferase Family 2 Member B28), spanning seven informative sequence variants across at least 14 kb, a deletion in USP17L2 (Ubiquitin Specific Peptidase 17-Like Family Member 2) spans three informative variants across at least 2 kb. Both deletions are present in the affected grand-mother and segregate in as many as four and five of her descendants respectively. Further in-depth analysis of normally segregating rare variants is ongoing.

These results implicate UGT2B28 and USP17L2 in the pathogenesis of endometriosis. UGT2B28 is phase II detoxification gene involved in glucuronidation of many substrates including steroid hormones and lipid-soluble drugs. USP17L2 is a deubiquitinase that regulates key cellular processes like proliferation, migration and apoptosis through the activation of small GTPases like RAC1A, CDCl42 and RHOA, and the regulation of adherence junctions. USP17L2 plays a central role in the regulation of the transcription factors SNAIL, SLUG and TWIST which are key gate-keepers of epithelial-to-mesenchymal transition (EMT). Dosage dependent loss of USP17L2 may affect mesothelial integrity and may increase the risk for developing endometriosis.

Example 11. Segregation Analysis of Families: Dominant Genes Contribute to Pathogenesis of Endometriosis

The largest endometriosis family reported to date: spanning 19 generations with 218 women with surgically confirmed endometriosis were utilized in this study. An autosomal major gene effect may be likely in this family. Risk of endometriosis in 123 smaller families with probands selected from the same time period and unrelated to the index pedigree were examined. A genetic segregation analysis was performed to identify large pedigrees with familial endometriosis, observe segregation patterns for surgical endometriosis, and compare segregation patterns with dominant patters seen in the 137 subject index pedigree.

Referring to FIG. 18, over 1900 women from Intermountain West US with surgically confirmed endometriosis were included in the study. A 3-generation pedigree was obtained for each affected woman. A genealogy database (GenDB) was utilized to find common ancestors linking one or more grandparents of probands. Probands with no genealogy available were eliminated. Probands with a birth date between 1960 and 1995 were selected arriving at an index pedigree of 89 subjects having surgically confirmed endometriosis and unrelated pedigree of 123 subjects having surgically confirmed endometriosis. Percentage of affected subjects in both the index pedigree and unrelated pedigrees is shown in FIG. 19 and the rate of surgically diagnosed endometriosis is shown in FIG. 20.

Referring to FIG. 17, prevalence of endometriosis in close relatives is much higher than the 2-3% prevalence of surgically diagnosed endometriosis in the general population. The rates observed are also higher than expected with multifactorial polygenic inheritance.

Analysis of larger number of families confirms that autosomal dominant, high penetrance risk alleles for endometriosis segregate in families. The heritability of endometriosis may be higher than estimated by older twin studies.

TABLE 1
Variants associated with endometriosis. Inf means that the variant was not
observed in the control cohort.
			Alter-
			nate
		Refer-	Allele/		Amino				OR
		ence	Minor		Acid	Case	Control	p	[L95-	Context	SEQ
Chr	Position	Allele	Allele	Gene	position	MAF	MAF	value	U95]	Sequence	ID NO
chr	113921	G	A	TNFRS	p.R175C	0.006	0.004	2.97	1.57	CCTGGGGAG	SEQ
1	6			F18		86	37	E-	[1.07-	GGGCTGGCT	ID
								02	2.31]	GCGGTCGGT	No:
										GGCCCCGGA	1
										GGAC[G/A]G
										CCAGGCTCA
										CACCCACAG
										GTCTCCCAG
										CCGCCCCTT
										CTC
chr	145259	T	C	ATAD3	p.W110R	0.007	0.000	2.93	19.2	GCTGGAAGC	SEQ
1	2			A		35	38	E-	4[11.	CCTGAGCCT	ID
								22	09-	GCTGCACAC	NO:
									33.3	ACTAGTCTG	2
									8]	GGCA[T/C]GG
										AGTCTCTGC
										CGTGCCGGA
										GCCGTGCAG
										ACACAGGAG
										CG
chr	370358	C	T	LRRC4	p.V301M	0.006	0.004	2.53	1.61	ACGTGCAGG	SEQ
1	9			7		62	12	E-	[1.09-	ACCCTGAGC	ID
								02	2.38]	AGCAGCCGG	No:
										CCGGCATCT	3
										CCCA[C/T]GT
										CCTGCTCCTC
										CCCATCACC
										ACCTTCCCG
										CCTCTGCTTC
chr	908311	G	T	SLC2A	p.T59	0.006	0.003	1.69	1.7[1	GAGCTTCCC	SEQ
1	2			7	N	13	61	E-	.14-	GTCCATGAA	ID
								02	2.55]	TGTTGCGTG	No:
										TCGCTCAAA	4
										GTAG[G/T]TT
										TCGTTGTAA
										AATGACTTG
										AAGACCTGG
										AAAACATTG
										CC
chr	105293	A	G	DFFA	p.I69T	0.007	0.005	4.67	1.46	ATTGGAAGG	SEQ
1	26					60	20	E-	[1.02-	TAGACACAG	ID
								02	2.1]	AAAGTAATC	No:
										GTCATCATC	5
										CACT[A/G]TG
										GTGCCATCC
										TCTGCCAGG
										ACCAGGGTG
										ACTGGTGTC
										AG
chr	119833	C	T	KIAA2	p.E410	0.005	0.003	1.44	1.72	ATCTGCTGG	SEQ
1	52			013	K	88	42	E-	[1.14-	ACGGAGGAC	ID
								02	2.61]	AGCCGCCCC	No:
										GGCCACAGG	6
										TTCT[C/T]GG
										CGTGCATGG
										TGGCGTGCC
										CGCTGAAGC
										AGTGATCTT
										CA
chr	128559	A	G	PRAM	p.N42	0.005	0.003	3.74	1.63	TCCTGCCCCT	SEQ
1	96			EF1	6D	39	31	E-	[1.06-	GAGGAGAGT	ID
								02	2.52]	TTGAATTCCT	No:
										TGGTTCGTG	7
										TC[A/G]ATTG
										GGAGATCTT
										CACCCCACT
										TCGGGCTGA
										GCTGATGTG
chr	128560	C	T	PRAM	p.G45	0.014	0.003	6.69	4.78	CACTGAGGG	SEQ
1	79			EF1	3G	22	01	E-	[3.6-	AAGTCAGGC	ID
								20	6.33]	AGCCCAAGA	No:
										GGATCTTCA	8
										TTGG[C/T]CC
										CACCCCCTG
										CCCTTCCTGT
										GGCTCATCA
										CCGTCTGAG
										G
chr	136692	C	T	PRAM	p.E352	0.006	0.000	5.37	201.	TGGGAGTAG	SEQ
1	76			EF14	K	86	03	E-	46[6	TGGATCTGA	ID
								35	1.22-	CAGCCCTCC	No:
									662.	AAGATGAGG	9
									92]	GTTT[C/T]GA
										GAGAGGCAG
										CAATTTTCTC
										TAGCAGAGC
										TCCGAGGGG
										T
chr	159869	A	T	RSC1A	p.N20	0.005	0.002	2.92	1.78	AACATAGGG	SEQ
1	77			1	51	205	931	E-	[1-	GACCTTGAG	ID
								02	2.94]	CTTCCTGAA	NO:
										GAAAGGCAA	10
										CAGA[A/T]TC
										AACACAAAA
										TTGTTGATTT
										GGAAGCTAC
										GATGAAAGG
										A
chr	176033	C	T	PADI3	p.H50	0.009	0.006	2.64	1.47	CCTGCTTCA	SEQ
1	40				8H	07	19	E-	[1.05-	AGCTCTTCC	ID
								02	2.05]	AGGAAAAGC	NO:
										AGAAGTGTG	11
										GCCA[C/T]GG
										GAGGGCCCT
										CCTGTTCCA
										GGGGGTTGT
										TGGTGGGTA
										AC
chr	194511	A	T	UBR4	p.A31	0.011	0.008	4.27	1.38	TTTCTGTTAG	SEQ
1	76				49A	27	21	E-	[1.02-	AAGCTGAGT	ID
								02	1.86]	ATAGGCCTC	No:
										AAACACATC	12
										AGC[A/T]GCA
										TGACCCTGG
										GAGAAGAAA
										ATTTGCATG
										AGAACCTGT
										G
chr	195040	T	C	UBR4	p.M84	0.011	0.008	4.24	1.38	CGAGCCAAG	SEQ
1	62				4V	27	1 9	E-	[1.03-	ATAAGCGGC	ID
								02	1.86]	ACGAAGCGC	No:
										ATCTGAGCA	13
										TCCA[T/C]GT
										TGACGCTCA
										ACTCCTGGA
										TGATCTGGA
										CAAAAAGCG
										AC
chr	195458	G	A	EMC1	p.Y96	0.011	0.008	2.81	1.4[1	TGGCAAAAA	SEQ
1	93				1Y	52	23	E-	.05-	CCAGGCCAA	ID
								02	1.89]	AGAGGACGC	No:
										TGCTGATTA	14
										ACAC[G/A]TA
										GTCATAGTC
										ATCCTTCAG
										AACGTCAAA
										CTGCTTGGA
										TG
chr	204428	C	T	PLA2G	p.G45	0.009	0.006	3.60	1.41	TCTTTGGGTT	SEQ
1	78			2D	S	80	95	E-	[1.03-	GGCCTCTGC	ID
								02	1.95]	CACCTAGTC	No:
										CGCAGTGAC	15
										AGC[C/T]GTA
										GGGCCAGTA
										GGAGAGGAT
										GGGCATTTT
										CCCAGTCAC
										T
chr	238455	A	T	E2F2	p.A25	0.011	0.008	4.78	1.35	CCTTGACGG	SEQ
1	89				7A	52	56	E-	[1.01-	CAATCACTG	ID
								02	1.81]	TCTGCTCCTT	No:
										AAAGTTGCC	16
										AAC[A/T]GCA
										CGGATATCC
										TGGTAAGTC
										ACATAGGCC
										AGCGTAGGG
										C
chr	244881	C	T	IFNLR	p.E137	0.009	0.006	3.42	1.46	TGCAGGGGG	SEQ
1	31			1	E	31	39	E-	[1.04-	GCAGCTGGT	ID
								02	2.05]	ACGTGGCAT	No:
										TGGCACTCA	17
										GGAT[C/T]TC
										CTCCGTCTG
										GGTGAGCAC
										CAGGACAGG
										TGGGGCCGG
										CT
chr	266088	A	G	UBXN	p.G49	0.008	0.000	5.67	44.6	CGGGACTGG	SEQ
1	83			11	0G	82	20	E-	2[23.	GGCCGGGAC	ID
								34	65-	CGGGACCGG	NO:
									84.2]	GACTGGGGC	18
										CGGG[A/G]CC
										GGGACCGGG
										ACAGGGACC
										AGGACTGAA
										TTTCAGGCT
										GG
chr	266714	G	C	AIM1L	p.P579	0.018	0.000	5.40	Inf	TGAGGCAGC	SEQ
1	13				R	63	00	E-		AGGAGCACC	ID
								89		AGGGCCCTT	NO:
										CACAACCTC	19
										TTTT[G/C]GG
										GTGGTGGAC
										AAGGCAGCA
										GGAGCACCA
										GACCCCTGC
										AC
chr	266716	A	G	AIM1L	p.S508	0.025	0.000	4.40	127.	CAGGAGCAC	SEQ
1	25				S	98	21	E-	41[5	TGGACCCCT	ID
								88	5.94-	GCACCACCT	NO:
									290.	CCTTCTGGG	20
									2]	TGGG[A/G]G
										ATGAGGCAG
										CAGGAGCAC
										CAGGGCCCT
										TCACGACCT
										CTT
chr	276743	G	A	SYTL1	p.A12	0.005	0.000	1.34	Inf	CCCAGGAGA	SEQ
1	34				6T	88	00	E-		CCAGGCTCC	ID
								35		AGGCCACGA	NO:
										CAGGGAGGC	21
										TGAG[G/A]CT
										GCTGTGAAA
										GAGAAGGAA
										GAGGGGCCA
										GAGCCCAGG
										TG
chr	289319	T	A	TAF12	p.T145	0.006	0.004	4.77	1.48	CCAGGGCTC	SEQ
1	01				S	86	65	E-	[1.01-	TGGCATTTC	ID
								02	2.17]	CTCACCTGTT	NO:
										TGTGAGCTT	22
										CTG[T/A]GGT
										GCAAGCTTT
										TTTGTAGGG
										TCGGATTTCT
										TCAGAGCCA
chr	294477	G	A	TMEM	p.C183	0.005	0.002	4.90	1.94	TACCCCGAC	SEQ
1	92			200B	C	64	91	E-	[1.27-	GCGGGGACG	ID
								03	2.97]	GGTCCCAGA	NO:
										TTTCTGGCTC	23
										TGC[G/A]CAG
										CCTACGGCT
										CGGGGACTC
										CTAGGGCCG
										GGGCTGGGA
										A
chr	314096	A	G	PUM1	p.A10	0.005	0.003	3.69	1.64	GGGGACCGT	SEQ
1	34				97A	39	29	E-	[1.07-	CGTTCATGG	ID
								02	2.53]	TGCACACCT	No:
										CATCGATGA	24
										GCAC[A/G]GC
										GCGCTCCGT
										ACGTGAGGC
										GTGAGTAAC
										ACACTTCTC
										CA
chr	353707	C	A	DLGA	p.G83	0.013	0.000	1.13	301.	TGGCCAGGG	SEQ
1	38			P3	W	24	04	E-	95[9	TACATCCTG	ID
								63	4.37-	GGGAAGGTG	No:
									966.	CTGCTACCC	25
									13]	CCCC[C/A]AA
										CCCCGGCCC
										CCGCTGGCC
										CTCCCTCAG
										GGCCTACCG
										AC
chr	405332	C	G	CAP1	p.C236	0.029	0.000	5.89	Inf	GACCCTCTG	SEQ
1	89				W	90	00	E-		CCGGATCAT	ID
								176		GTCCTCCTCC	No:
										CCCTCCACC	26
										ATG[C/G]CCC
										CCTCCTCCCC
										CAGTCTCTA
										CCATTTCAT
										GCTCATATG
chr	407023	A	G	RLF	p.T656	0.011	0.007	3.11	1.41	TGAATGACC	SEQ
1	42				T	03	87	E-	[1.04-	AAGCCAAAG	ID
								02	1.9]	GAGAGTCTC	No:
										ATGAATATG	27
										TCAC[A/G]TT
										CAGCAAATT
										AGAAGATTG
										CCACCTGCA
										AGACAGAGA
										TT
chr	409289	A	G	ZFP69	p.Q43	0.006	0.004	1.30	1.67	AGTAAAACC	SEQ
1	69			B	8R	86	12	E-	[1.14-	TTCAGCCAT	ID
								02	2.45]	AGTACATAC	No:
										CTAACTCAA	28
										CACC[A/G]GA
										GAACTCATA
										CTGGAGAAA
										GACCATATA
										AATGTAAGG
										AA
chr	476914	G	C	TAL1	p.A27	0.005	0.000	6.06	460.	CTCCTTGGC	SEQ
1	81				G	15	01	E-	35[6	GACGCCGTT	ID
								28	1.91-	CAGCAGGAC	No:
									3423	CAGGTGCGG	29
									.16]	GGGG[G/C]CC
										ATGCTGGCC
										TCGGCCGCG
										TCCCGTCCCT
										CTAGCTGGG
										G
chr	477168	C	T	STIL	p.T126	0.009	0.006	4.22	1.41	AGAAGGTGC	SEQ
1	89				2T	56	79	E-	[1.02-	CTACTGAAT	ID
								02	1.95]	TCATGCTATT	No:
										CATCTGCTTT	30
										AG[C/T]GTTT
										CAGAAGGTT
										GCAAACTTT
										CAGGAAAAA
										TTGTAATGT
chr	556436	T	C	USP24	p.T158	0.007	0.004	4.65	1.51	GTTCTAAGG	SEQ
1	58				A	11	71	E-	[1.03-	TCTGAAAAC	ID
								02	2.22]	TTACCAAGT	No:
										CTTGCTAGG	31
										TAGG[T/C]AG
										ATGCCAACA
										GGCATTTGC
										CTAGTGATT
										CTTCTCGCTT
										G
chr	953304	C	T	SLC44	p.N42	0.006	0.004	2.78	1.57	TGGTGAGGA	SEQ
1	40			A3	4N	62	23	E-	[1.06-	TTCCGAGAA	ID
								02	2.32]	TCATTGTCAT	No:
										GTACATGCA	32
										AAA[C/T]GCA
										CTGAAAGAA
										CAGGTAAGG
										CTACCTCCT
										GATACACAG
										C
chr	109792	T	C	CELSR	p.L17P	0.009	0.000	2.93	21.0	CCGGCCACC	SEQ
1	751			2		80	47	E-	6[13.	GGCGTCCCC	ID
								32	61-	CTCCCAACG	No:
									32.5	CCGCCGCCG	33
									9]	CCGC[T/C]GC
										TGCTGCTGTT
										GCTGCTGCT
										GCTGCCGCC
										GCCACTATT
										G
chr	110302	A	T	EPS8L	p.F55I	0.006	0.003	3.20	1.92	AAGTCTTGG	SEQ
1	392			3		13	20	E-	[1.28-	CTCCACACC	ID
								03	2.88]	CGGCCCTGT	No:
										GCATCCATC	34
										TCGA[A/T]CA
										GCTTCTGCA
										AGGCATCCT
										CGGGCCCCT
										GGACTCTCT
										GA
chr	117122	T	C	IGSF3	p.K10	0.025	0.000	1.05	Inf	CTTTCCTCTT	SEQ
1	350				20E	25	00	E-		CCTGTTCTTC	ID
								150		CAGGCCAGG	No:
										GCTGCTCCTT	35
										T[T/C]CCCCC
										CAGCTTTAG
										TCCTCAGGG
										AATACCAGG
										CCACAGCG
chr	120054	G	T	HSD3	p.R71I	0.010	0.007	1.85	1.48	GTGCTGGAA	SEQ
1	192			B1		54	17	E-	[1.08-	GGAGACATT	ID
								02	2.01]	CTGGATGAG	NO:
										CCATTCCTG	36
										AAGA+G/T+A
										GCCTGCCAG
										GACGTCTCG
										GTCATCATC
										CACACCGCC
										TGT
chr	144856	C	T	PDE4	p.A21	0.009	0.005	1.71	1.54	TTACCTCTGT	SEQ
1	852			DIP	05A	07	92	E-	[1.1-	GCCTTGGGC	ID
								02	2.14]	TTCAAGGCC	NO:
										AGGGAAGCT	37
										GCA[C/T]GCT
										GATCTCACA
										AGAGACACT
										ATCTTTTTGA
										CCAGCAGCT
chr	144912	G	T	PDE4	p.P695	0.005	0.002	5.35	2.39	ACAGCCAGT	SEQ
1	191			DIP	H	15	16	E-	[1.53-	GGGGGTAAC	ID
								04	3.74]	TTCAGCTTGT	NO:
										TGGTTAGAG	38
										ATG[G/T]GTG
										CTTGGGACA
										TCAGGGAGT
										CTCTCCCTCC
										TAAATATTG
chr	144930	A	C	PDE4	p.S244	0.007	0.004	7.25	1.73	CTTTCTGTTG	SEQ
1	977			DIP	S	35	27	E-	[1.19-	TGGAGGGCT	ID
								03	2.5]	AGCCTGGAC	NO:
										GCTTGCATC	39
										CAA[A/C]GAT
										TCCACAGAG
										GAACCAGGC
										GTCTCTTCCT
										CCATGCTTT
chr	145537	C	A	ITGA10	p.S841	0.009	0.006	2.01	1.5[1	CAACTCTGG	SEQ
1	513				R	31	22	E-	.08-	AGAACAGAA	ID
								02	2.09]	AGGAAAATG	NO:
										CTTACAATA	40
										CGAG[C/A]CT
										GAGTCTCAT
										CTTCTCTAG
										AAACCTCCA
										CCTGGCCAG
										TC
chr	149897	G	A	SF3B4	p.P245	0.007	0.005	2.66	1.52	GGGGTATCC	SEQ
1	906				P	84	17	E-	[1.06-	CAGGTGGGA	ID
								02	2.18]	GGGCTCCAG	NO:
										GAGGTGGCA	41
										CTGG[G/A]GG
										TGGGAAGGA
										GCCAGGAGG
										AGGCATGCC
										TATAGAGGA
										AA
chr	152080	C	T	TCHH	p.E180	0.010	0.000	2.67	Inf	TTCCGTCAC	SEQ
1	275				6E	54	00	E-		GCTGTTGGG	ID
								63		GGCGCAGCT	NO:
										GCTGTTCTTC	42
										CCT[C/T]TCC
										TGGCGTAGC
										TGTTCCTCCT
										CGCGGAATT
										TTCTGTCAG
chr	152082	T	C	TCHH	p.K10	0.013	0.000	1.95	28.9	CTCAGCAGC	SEQ
1	449				82E	24	46	E-	5[19.	TGCTCTTCCT	ID
								48	46-	CCTGCTGCA	NO:
									43.0	GCTCCTCTTC	43
									5]	CT[T/C]CCGA
										TATTGCCTCT
										CCAGCTCCT
										GGCGCCTTC
										TCGTCTCC
chr	152083	G	T	TCHH	p.P789	0.010	0.000	1.16	Inf	CTCCTCGGC	SEQ
1	327				Q	29	00	E-		CCTCAGCTG	ID
								61		CCTCTCCCG	NO:
										CTGCTCCCG	44
										CAAT[G/T]GG
										GGCCTGGCC
										GACAGCCTC
										TGACGGCCC
										CTCTCGCTCT
										T
chr	152083	G	T	TCHH	p.R622	0.019	0.000	1.65	Inf	TTCAGCAGC	SEQ
1	829				S	36	00	E-		TGCTGGCGC	ID
								115		CTCTCTTCCT	NO:
										CCGGCTCCT	45
										CGC[G/T]CTT
										CAGCCGCTG
										CTCGCGCCT
										CTCCTCCTGC
										TCGAGTCTC
chr	152084	C	G	TCHH	p.E494	0.014	0.000	4.56	164.	AGTTGCTGC	SEQ
1	213				Q	71	09	E-	52[7	TCGCGCCTC	ID
								70	5.16-	TCCTGCTGCT	NO:
									360.	CGCGCCTCT	46
									14]	CCT[C/G]CTC
										CTCGAGCTT
										CAGCCAACG
										TTCGCGCCT
										CTCCTCCTCC
chr	152325	G	C	FLG2	p.T169	0.007	0.000	1.95	799.	TAATCCATG	SEQ
1	166				9R	11	01	E-	16[1	ATGATAGTG	ID
								41	08.8	GGCATGTCT	No:
									4-	AGTGGTATC	47
									5868	TCCT[G/C]TC
									.08]	TGTCCATGA
										GTAGTTCCA
										TGTCTCTCA
										GGAACTATG
										GA
chr	156011	G	A	UBQL	p.P514	0.005	0.003	3.43	1.63	CTGTTGGAG	SEQ
1	387			N4	P	15	16	E-	[1.05-	AAGATGTGG	ID
								02	2.54]	CTGGCGTGG	No:
										CTGGTGAGG	48
										AAGT[G/A]G
										GGGCCTCGG
										GCGTAGACC
										CTGCGTTGC
										TGCCTGCTG
										AGG
chr	156046	T	C	MEX3	p.G48	0.005	0.002	1.14	1.82	CGCAGATGC	SEQ
1	473			A	5G	15	83	E-	[1.17-	GTACTGCAC	ID
								02	2.84]	ACTCCATGC	No:
										AGAACAGGT	49
										TGTG[T/C]CC
										GCAGGGCAC
										AAGGGCGGC
										AGTCACTTC
										GCTCTCAAA
										GC
chr	156438	C	T	MEF2	p.Q38	0.010	0.000	2.23	1107	GTTGCGGCT	SEQ
1	664			D	5Q	05	01	E-	.97[1	GCTGAGGCT	ID
								58	52.3	GCTGTGGCT	No:
									7-	GTGGCTGCT	50
									8056	GTGG[C/T]TG
									.7]	CGGTGGCTG
										CTGCTGTGG
										AGGCTGTGG
										CTGCTGCGG
										CT
chr	156521	C	T	IQGAP	p.A56	0.005	0.003	3.53	1.6[1	TGCCTTTTGG	SEQ
1	547			3	2T	88	68	E-	.06-	CTGCCACAA	ID
								02	2.42]	GGAGGAGAT	No:
										GGTACCGAG	51
										GGG[C/T]GAC
										AGGGAGGCT
										GACATCATC
										TAGGCCAGC
										TGCAGGAAG
										C
chr	156779	G	A	SH2D2	p.G29	0.006	0.003	1.36	1.7[1	CCACATAGA	SEQ
1	118			A	3G	37	76	E-	.14-	TGTTGCTGG	ID
								02	2.53]	GGGCTTCCC	No:
										CAGGGCTGC	52
										CCCG[G/A]CC
										CATGGCATA
										GAAAGCTAT
										GGGTTCATC
										AGGCTCATT
										GT
chr	157069	G	A	ETV3L	p.S32L	0.012	0.008	3.56	1.37	GATGAAGTG	SEQ
1	134					25	99	E-	[1.03-	CCACAGCTG	ID
								02	1.82]	GATCTGCCG	No:
										GGAGCCTGG	53
										GGAC[G/A]A
										CTCGGCTTT
										GTAGGCCCA
										ATCAGGGAA
										GGCCAACCC
										TGG
chr	157738	G	T	FCRL2	p.L260	0.005	0.001	6.20	2.69	TATTTGCCG	SEQ
1	309				M	21	94	E-	[1.51-	GCATCACTC	ID
								04	4.48]	TCTTTCACA	NO:
										GCTGGGATC	54
										TCCA[G/T]CT
										CTGCTGACA
										GGGAACGCT
										GGGTTTTCTT
										TCCCATACT
										G
chr	158669	G	C	OR6K2	p.A22	0.005	0.000	3.16	596.	TGTGCGGCG	SEQ
1	772				4G	39	01	E-	28[8	GCCTCCAGC	ID
								31	0.36-	TGAATGAAT	NO:
									4424	ACGTAGAAT	55
									.77]	TACA[G/C]CC
										ACAATACCA
										TCGTAGGAC
										ATGAAGATG
										AGCATCACA
										GC
chr	161336	A	G	C1orf1	p.Y10	0.005	0.003	2.89	1.66	GAGACCAGT	SEQ
1	289			92	Y	64	41	E-	[1.09-	TCTGCAGAT	ID
								02	2.53]	ACTTGGATG	NO:
										AGAAAGCCT	56
										TTTC[A/G]TA
										CTGTGGAGA
										GAAAGATAA
										GTAGCCCTA
										TGAGACTTC
										AA
chr	161476	C	T	FCGR	p.S69S	0.005	0.003	4.84	1.61	CTGTGACTC	SEQ
1	227			2A		15	20	E-	[1.04-	TGACATGCC	ID
								02	2.5]	AGGGGGCTC	NO:
										GCAGCCCTG	57
										AGAG[C/T]GA
										CTCCATTCA
										GTGGTTCCA
										CAATGGGAA
										TCTCATTCCC
										A
chr	161641	G	A	FCGR	p.Q63	0.010	0.003	2.83	3.19	CTGTGCTGA	SEQ
1	237			2B	Q	78	40	E-	[2.33-	AACTCGAGC	ID
								10	4.37]	CCCAGTGGA	NO:
										TCAACGTGC	58
										TCCA[G/A]GA
										GGACTCTGT
										GACTCTGAC
										ATGCCGGGG
										GACTCACAG
										CC
chr	169697	A	G	SELE	p.L404	0.005	0.003	3.16	1.67	TCCCCTGTG	SEQ
1	268				L	15	10	E-	[1.07-	GGGCCACAT	ID
								02	2.59]	TGGAGCCTT	NO:
										TTGGATCCC	59
										TTCA[A/G]CA
										CAAAACCCT
										GCTCACAGG
										AGAACTCAC
										AGCTGGACC
										CA
chr	170115	G	C	METT	p.D18	0.000	0.000	1.00	1[0.3	GGGAGCCCA	SEQ
1	300			L11B	H	74	74	E+00	1-	TTTTGCCTTT	ID
									3.22]	AGATCCCGC	NO:
										TGGCAGAAG	60
										ACC[G/C]ACG
										ATGAACTCT
										GTAGACATA
										GCATGTCTTT
										TATCCTTCA
chr	170129	T	C	METT	p.M66	0.008	0.006	1.44	1.29	AAATTGTAC	SEQ
1	701			L11B	T	82	84	E-	[0.92-	GCTTTAACA	ID
								01	1.82]	AGCCAAGTC	NO:
										ATCAATGGT	61
										GAGA[T/C]GC
										AGTTCTATG
										CCAGAGCTA
										AACTTTTCTA
										CCAAGAAGT
										A
chr	170136	T	C	METT	p.L277	0.010	0.010	1.00	0.99	GGCTTCCCA	SEQ
1	876			L11B	P	78	87	E+00	[0.73-	GAGCAGTGC	ID
									1.35]	ATCCCCGTG	NO:
										TGGATGTTC	62
										GCAC[T/C]GC
										ACAGCGACA
										GACACTCCT
										GAAAAAGCA
										GTGGGAATG
										AA
chr	176563	G	A	PAPP	p.V34	0.008	0.005	2.96	1.51	GCGGGATGC	SEQ
1	779			A2	7M	09	37	E-	[1.06-	TCGCTTCTTC	ID
								02	2.15]	TTCTCCCTCT	NO:
										GCACCGACC	63
										GC[G/A]TGAA
										GAAAGCCAC
										CATCTTGATT
										AGCCACAGT
										CGCTACCA
chr	176833	T	C	ASTN1	p.E129	0.006	0.003	1.03	1.72	TCATTCTGG	SEQ
1	427				3G	62	85	E-	[1.17-	CAGCAGCTC	ID
								02	2.54]	CCTGGCCTT	NO:
										ATGGTGCTA	64
										GATC[T/C]CT
										TTGCTGTCCC
										CATAGTCGT
										TGTAGGGGA
										TACTCAGGG
										T
chr	176833	C	T	ASTN1	p.T127	0.006	0.004	4.58	1.52	CATAGTCGT	SEQ
1	480				5T	13	04	E-	[1.02-	TGTAGGGGA	ID
								02	2.28]	TACTCAGGG	NO:
										TCTGCTCCTC	65
										ACA[C/T]GTC
										TTCCTGAGG
										TCCCGGCTG
										AGCTCCGCC
										CAGTCAAGT
										C
chr	176852	T	G	ASTN1	p.M10	0.006	0.003	4.39	1.54	GAGATGGTG	SEQ
1	074				95L	13	99	E-	[1.03-	GTGAGCTGC	ID
								02	2.3]	TTGTCCGGC	No:
										ACCTGAGAT	66
										GGCA[T/G]TG
										CACAAGGAG
										ACTTTGCTCC
										AGAGATGAT
										GTCGTCCAC
										A
chr	186276	G	A	PRG4	p.E473	0.006	0.000	3.12	Inf	TACACCCAC	SEQ
1	268				K	62	00	E-		CACTCCCAA	ID
								39		GGAGCCTGC	No:
										ACCCACCAC	67
										CAAG[G/A]A
										GCCTGCACC
										CACCACTCC
										CAAAGAGCC
										TGCACCCAC
										TGC
chr	198222	C	G	NEK7	p.R35	0.012	0.008	2.08	1.42	CTTACGACC	SEQ
1	215				G	25	67	E-	[1.07-	GGATATGGG	ID
								02	1.89]	CTATAATAC	No:
										ATTAGCCAA	68
										CTTT[C/G]GA
										ATAGAAAAG
										AAAATTGGT
										CGCGGACAA
										TTTAGTGAA
										GT
chr	201178	A	G	IGFN1	p.E155	0.009	0.000	6.26	Inf	GGGAGTAAG	SEQ
1	688				6G	80	00	E-		GCAGGTTTT	ID
								47		ACGGATGGT	No:
										TTAGGAGGT	69
										TCTG[A/G]AG
										AAATGGGGT
										CAGTGAATA
										AGGCAGGTT
										ATAGGAAGG
										AT
chr	201180	A	G	IGFN1	p.N20	0.008	0.000	6.77	476.	TAGGGATGG	SEQ
1	217				66D	58	02	E-	2[65.	TTTAGGGAG	ID
								40	22-	TTCTGTAGA	No:
									3476	AATGGGGTC	70
									.77]	AGTG[A/G]AT
										GAGGCAGGT
										TATAGGAAG
										GATTTAGGG
										GCTCCTAAG
										GG
chr	203194	C	T	CHIT1	p.E74	0.006	0.003	9.72	1.74	CACATCTTCT	SEQ
1	834				K	62	80	E-	[1.18-	TCAGGCCAT	ID
								03	2.58]	TGAACTCCT	No:
										GGTAGAGAG	71
										TCT[C/T]GTC
										ATTCCACTC
										AGTGGTGCT
										CAGCTGGTG
										GTTGGTCAT
										G
chr	203691	A	G	ATP2B	p.K94	0.005	0.002	4.39	2.02	ACTTAACCT	SEQ
1	612			4	0R	15	55	E-	[1.3-	CCAGTGCTT	ID
								03	3.15]	CTCCTCTCCC	No:
										CACTAGGTG	72
										AGA[A/G]ATT
										CTTTGATATT
										GATAGTGGG
										AGGAAGGCA
										CCTCTACAT
chr	204923	G	A	NFAS	p.D81	0.005	0.000	3.59	Inf	CCACTGGAC	SEQ
1	359			C	N	64	00	E-		ACGAAACAG	ID
								34		CAGATTCTT	No:
										CAACATCGC	73
										CAAG[G/A]A
										CCCCCGGGT
										GTCCATGAG
										GAGGAGGTC
										TGGGACCCT
										GGT
chr	204923	C	T	NFAS	p.R115	0.005	0.000	1.05	Inf	GCGGCCGGA	SEQ
1	461			C	C	39	00	E-		GGAATATGA	ID
								32		GGGGGAATA	No:
										TCAGTGCTT	74
										CGCC[C/T]GC
										AACAAATTT
										GGCACGGCC
										CTGTCCAAT
										AGGATCCGC
										CT
chr	206658	G	A	IKBKE	p.T514	0.010	0.006	2.08	1.47	AGCTAGCGG	SEQ
1	569				T	05	84	E-	[1.07-	AGGTCCTCT	ID
								02	2.02]	CCAGATGCT	No:
										CCCAAAATA	75
										TCAC[G/A]GA
										GACCCAGGA
										GAGCCTGAG
										CAGCCTGAA
										CCGGGAGCT
										GG
chr	222712	G	T	HHIPL	p.L487	0.010	0.006	1.35	1.71	ACTGACTTC	SEQ
1	108			2	M	78	33	E-	[1.26-	CCCACTGCA	ID
								03	2.32]	TGGCCATAA	No:
										GCATAGATT	76
										GGCA[G/T]AA
										CATCATCTG
										TCCAGGAGA
										GAGGAAAGA
										GAGTGAGTG
										TC
chr	227843	T	A	ZNF67	p.F413	0.009	0.000	1.18	1063	GGAGAGAAA	SEQ
1	024			8	Y	56	01	E-	[146.	CCCTACAAA	ID
								55	01-	TGTGAAGAA	No:
									7739	TGTGGCAGA	77
									.02]	ACCT[T/A]TA
										CTCAATTCTC
										AAACCTCAC
										TCAGCATAA
										AAGAATTCA
										T
chr	231057	C	T	TTC13	p.G55	0.012	0.000	5.31	Inf	TTTCTCAAA	SEQ
1	248				3D	99	00	E-		ATATTCTAG	ID
								75		GTATCTCAT	No:
										GTTGATCAC	78
										CTGA[C/T]CC
										CTATAAGGC
										AAAAATAAT
										AAAATTAAG
										AATATTTTTA
										T
chr	236144	G	T	NID1	p.S107	0.005	0.002	8.73	1.93	AGAGATGCA	SEQ
1	919				3S	15	68	E-	[1.24-	CACACATAT	ID
								03	3]	TTACACAAA	No:
										GATACCCTC	79
										TCAC[G/T]GA
										ATCCGTTAC
										AATGCCTCT
										GGGATTCAC
										CAAGTCAGT
										CT
chr	236433	T	G	ERO1L	p.K63	0.005	0.003	3.47	1.62	ACCTTACCTT	SEQ
1	208			B	N	88	65	E-	[1.07-	GTAATAACG	ID
								02	2.44]	AAAATAGTC	No:
										TCTCTCTTGC	80
										AA[T/G]TTTT
										TTATTTTGGG
										GAAGATTTT
										GTAGGTATT
										GAAGTTAT
chr	246907	A	G	SCCP	p.I183	0.005	0.002	2.17	1.91	TCTTTTAGGT	SEQ
1	410			DH	V	21	73	E-	[1.08-	ACTTTGACT	ID
								02	3.17]	GCTGTGGAA	No:
										AGTTTCCTG	81
										ACT[A/G]TAC
										ATTCAGGAC
										CTGAGGTTG
										GTTTTTTGGT
										TTGTCTTGT
chr	248436	G	A	OR2T3	p.N28	0.008	0.002	5.54	3.43	CTCCCTTCAC	SEQ
1	265			3	4N	33	45	E-	[2.4-	CTCACTGTTC	ID
								09	4.9]	TTCACACTG	No:
										TAGATGAGG	82
										GG[G/A]TTTA
										GTAAAGGGG
										TGAACATAG
										TATAGAAGG
										CTGACACAA
chr	592504	G	A	ANKR	p.F257	0.005	0.003	2.59	1.66	TGGCTCTCA	SEQ
10	7			D16	F	39	25	E-	[1.08-	CATCTACAT	ID
								02	2.56]	CGACGCCAA	No:
										GTTCAGAGA	83
										CCAA[G/A]A
										ATCGGATGG
										CTTCGTCCTG
										CCCTGTGAC
										AGCTGCCCT
										GT
chr	597922	C	G	FBXO	p.A96	0.005	0.003	1.08	1.79	AGCGCACTG	SEQ
10	2			18	3A	64	16	E-	[1.17-	TGGAGAACA	ID
								02	2.73]	TCGTACTGC	No:
										CCCGGCATG	84
										AGGC[C/G]CT
										GCTCTTCCTC
										GTCTTCTGA
										GGACAAGGC
										GCACGTTCT
										C
chr	777195	C	T	ITIH2	p.N44	0.006	0.003	2.30	1.61	AACTAAAAC	SEQ
10	8				1N	37	96	E-	[1.09-	TGTCAAAAA	ID
								02	2.4]	TTCAGAAAA	No:
										ACGTTAAGG	85
										AGAA[C/T]AT
										CCAAGACAA
										TATCTCCTTG
										TTCAGTTTG
										GGCATGGGA
										T
chr	210975	G	A	NEBL	p.S885	0.006	0.004	3.59	1.55	TGACCTGTC	SEQ
10	46				F	37	13	E-	[1.04-	GTCTCCGAG	ID
								02	2.3]	ACCTGTACC	No:
										GAAAGTACT	86
										GCTG[G/A]AA
										TGGGATCGA
										GACCAGTGT
										CGCCTATAG
										TGACTCGCC
										TT
chr	345587	C	T	PARD	p.G10	0.005	0.002	1.96	1.74	CTAGCGTTG	SEQ
10	15			3	17R	15	97	E-	[1.12-	AGAGCCATG	ID
								02	2.7]	GAACCTTCA	No:
										TAAGAAGAA	87
										ACTC[C/T]CC
										CATACATTA
										ACTCATCAT
										CACAGCCAA
										ATGTCCGAT
										GA
chr	353221	C	T	CUL2	p.M34	0.009	0.004	5.26	2.06	TACCATGCA	SEQ
10	99				8I	778	78	E-	[1.37-	CTTCCAAAA	ID
								04	2.98]	CTGACTCCA	No:
										CAAATAGTG	88
										TTGG[C/T]AT
										CTAAAAATG
										AAATATAAG
										TACAAAACC
										ACATTTTAA
										GA
chr	454730	C	G	C10orf	p.M14	0.019	0.000	7.99	2197	CAGGCATCC	SEQ
10	44			10	5I	36	01	E-	.65[3	TGGCTTCAC	ID
								114	05.6	AGAGCCTCC	No:
									9-	CTCTGGGGG	89
									1579	CCCC[C/G]AT
									9.34]	GGGCTTGCT
										GCTGTCCAT
										CTGTCTATGT
										GGACCCCAG
										A
chr	469992	G	A	GPRIN	p.R110	0.007	0.005	3.98	1.46	AATGTGTCC	SEQ
10	09			2	Q	84	38	E-	[1.02-	ACCATGGGC	ID
								02	2.09]	GGCAGTGAC	No:
										CTGTGTCGC	90
										CTGC[G/A]GG
										CCCCTAGTG
										CTGCTGCTA
										TGCAGAGGA
										GCCATTCAG
										AC
chr	469993	A	G	GPRIN	p.A17	0.010	0.003	4.09	2.99	AGCCAGGTG	SEQ
10	90			2	0A	29	47	E-	[2.17-	GTACTTCTG	ID
								09	4.12]	GCCAGGGTG	No:
										GCCAGGCCC	91
										CTGC[A/G]GG
										CCTGGAAAG
										GGACCTGGC
										TCCTGAGGA
										TGAGACTTC
										TA
chr	470872	G	C	LOC10	p.L172	0.006	0.003	3.19	1.88	GGATTGTGC	SEQ
10	99			0996758	L	62	53	E-	[1.27-	TCATCTGGG	ID
								03	2.78]	TCATTGCCT	No:
										GTGTCCTCTC	92
										CCT[G/C]CCC
										TTCCTGGCC
										AACAGCATC
										CTGGAGAAT
										GTCTTCCAC
										A
chr	518279	A	G	FAM2	p.P13P	0.022	0.002	5.96	9.18	TGCAGATGA	SEQ
10	00			1A		30	48	E-	+7.2-	ACCGGACGA	ID
								49	11.7	CCCCCGACC	No:
										AGGAGCTGG	93
										CGCC[A/G]GC
										GTCGGAGCC
										CGTGTGGGA
										GCGGCCGTG
										GTCGGTGGA
										GG
chr	734648	G	A	CDH2	p.E960	0.008	0.004	2.90	1.94	GGTGGTCAC	SEQ
10	12			3	K	133	201	E-	[1.24-	CACCACCGA	ID
								03	2.91]	GCTGGACCG	No:
										CGAGCGCAT	94
										CGCG[G/A]A
										GTACCAGCT
										GCGGGTGGT
										GGCCAGTGA
										TGCAGGCAC
										GCC
chr	750106	G	C	MRPS	p.T130	0.008	0.004	8.85	1.74	CTAAAGTCA	SEQ
10	35			16	R	458	873	E-	[1.13-	GCTCATTTAT	ID
								03	2.59]	GTTTCTGTA	No:
										GCCTCTGTA	95
										TCT[G/C]TAG
										CTTCTGCATC
										TGTTTTCTGA
										GAAGCTAAC
										AGGACTTC
chr	795887	G	A	DLG5	p.A74	0.007	0.004	8.01	1.69	GGGACCCTT	SEQ
10	06				1A	35	35	E-	[1.17-	CTTTAGCGG	ID
								03	2.45]	CAGGGCTTC	No:
										CAGGCAGCA	96
										CAGC[G/A]GC
										AGCATACAC
										TCCATTCTCC
										AGACTGATG
										CCACTGTCT
										G
chr	995312	C	T	SFRP5	p.D10	0.010	0.006	2.15	1.46	CAGACGGGC	SEQ
10	84				3N	05	89	E-	[1.07-	GCAAAGAGC	ID
								02	2.01]	GAGCACAGG	No:
										AAGACCTGC	97
										GTAT[C/T]CG
										AGTGGCAGC
										GCTTGGCCA
										GCAGCGGCA
										GCCAGCTGC
										TC
chr	999696	A	G	R3HC	p.L593	0.006	0.003	2.22	1.91	TGTTTAACG	SEQ
10	50			C1L	L	86	60	E-	[1.3-	ATGATGGTG	ID
								03	2.81]	ACTGCCTGG	No:
										ATCCACGTC	98
										TTCT[A/G]CA
										AGAGGTATG
										TTTAATTGA
										AATTGCTTG
										ATGCTTAGT
										TA
chr	102770	A	G	PDZD	p.R777	0.011	0.000	2.35	126.	ACTTGCCTT	SEQ
10	315			7	R	03	09	E-	17[4	GACCCCGGC	ID
								44	5.36-	TGCTGCGGC	No:
									350.	TGCGGCTGC	99
									99]	GGCT[A/G]CG
										GCTGCGGCT
										ACGGCTCTG
										AGCCCGGCC
										CCGGATCTG
										GC
chr	104230	G	A	THEM	p.T139	0.010	0.007	4.44	1.39	AGTTCTTGCT	SEQ
10	587			180	T	54	62	E-	[1.02-	GTGCCTGTG	ID
								02	1.89]	CCTCTATGA	No:
										TGGCTTCCT	100
										GAC[G/A]CTC
										GTGGACCTG
										CACCACCAT
										GCCTTGCTG
										GCCGACCTG
										G
chr	125780	G	C	CHST1	p.P453	0.008	0.000	3.19	793.	GCTCCTTCTG	SEQ
10	760			5	P	58	01	E-	53[1	CCAGGGGCC	ID
								47	08.6	AGCTCGGGG	No:
									9-	GGTACGGGG	101
									5793	GGG[G/C]GG
									.56]	GGTACACAC
										AGGCATGGC
										GTTGTTGAG
										GGTGTTGTT
										GT
chr	135106	G	A	TUBG	p.H36	0.005	0.003	2.61	1.66	CCTGCGCCT	SEQ
10	137			CP2	0H	39	26	E-	[1.08-	GGCTGTCCC	ID
								02	2.55]	CTGTGTAGC	No:
										TGAAGCTCC	102
										TGTC[G/A]TG
										GAGCAGGCT
										CAGCGTGGA
										CCCCCCAAG
										ACATTCGCC
										TT
chr	135368	G	C	SYCE1	p.V28	0.008	0.005	2.96	1.51	GGCCAGCCT	SEQ
10	906				9V	09	37	E-	[1.06-	CTTCCTCTTG	ID
								02	2.15]	TGTGCTCTG	No:
										GGCTTGGGC	103
										AGG[G/C]ACT
										TGCATTCCA
										TGCTTTTCCA
										GCTCTTCCTT
										CAGCCTGG
chr	394511	C	T	PKP3	p.A73	0.006	0.000	6.27	Inf	AGCCGCGGC	SEQ
11					A	86	00	E-		ACAACGGGG	ID
								11		CCGCTGAGC	No:
										CCGAGCCTG	104
										AGGC[C/T]GA
										GACTGCCAG
										AGGTAGGCG
										GTGGGGACA
										GCGGCGGGG
										AT
chr	610300	A	G	PHRF	p.S145	0.006	0.003	2.18	1.93	CACAGGGGT	SEQ
11				1	5G	86	57	E-	[1.3-	CAGGCAGGT	ID
								03	2.85]	GTTCTCCGA	No:
										GCTGCCCTTT	105
										CCC[A/G]GTC
										ACGTGCTTC
										CGGAACCCG
										GGTTCCCAG
										ACACAGACC
										C
chr	614967	C	G	IRF7	p.R88	0.005	0.000	4.94	Inf	GCGCTCCGC	SEQ
11					T	88	00	E-		AGTCTCAGC	ID
								32		CTCGGGGGG	No:
										CGGGCCACC	106
										TCCC[C/G]TG
										CTGCTAGGC
										GGCCACCTG
										CCGCGGGCC
										ACAGCCCAG
										GC
chr	764414	A	G	TALDO1	p.K32	0.006	0.003	1.66	1.71	CTCTCTGAC	SEQ
11					1R	13	59	E-	[1.14-	GGGATCCGC	ID
								02	2.56]	AAGTTTGCC	No:
										GCTGATGCA	107
										GTGA[A/G]GC
										TGGAGCGGA
										TGCTGACAG
										TGAGTGTTG
										TGTGTGGGT
										AC
chr	101685	G	A	MUC6	p.P198	0.011	0.000	1.29	Inf	GGATAGGTA	SEQ
11	4				3S	27	00	E-		GTGGTGGTC	ID
								67		TGGAAGGAT	NO:
										GTTGCAGTC	108
										ATAG[G/A]AC
										CTGTGGAAG
										AGAAGGGAC
										TGCTCCCTGT
										AGGTGGGGA
										G
chr	101708	G	A	MUC6	p.P190	0.007	0.001	3.28	4.53	GGTAGGGAT	SEQ
11	5				6S	84	74	E-	[3.11-	GTAGAAGTT	ID
								11	6.59]	TTGGCCGTG	NO:
										CTAAATGAG	109
										CTTG[G/A]GG
										ATTGGCTGG
										TCCCACTGG
										TGGTCGGTG
										TCATTGGTG
										GG
chr	101754	G	A	MUC6	p.T175	0.025	0.000	8.09	Inf	GGTAGAAGT	SEQ
11	3				3I	25	00	E-		TGAGGTGAC	ID
								151		TTCAGGATG	No:
										GTGTGTGGA	110
										GGAA[G/A]T
										GTGTGAATG
										TAGGGATGT
										AGAGGTTTT
										GGCCGTGCT
										AAA
chr	101776	T	C	MUC6	p.Q16	0.009	0.000	1.12	180.	GGGATGTAG	SEQ
11	1				80Q	80	05	E-	29[7	AGGTTTTGG	ID
								51	6.39-	CTGTGTTTA	No:
									425.	ATGAGCTCA	111
									47]	GGGC[T/C]TG
										GCTGGTCCC
										GCTGGTGGT
										CAGCGTCAT
										TGTTGGCGC
										TG
chr	101778	C	T	MUC6	p.T167	0.009	0.000	1.86	27.7	TTAATGAGC	SEQ
11	5				2T	80	36	E-	8[17.	TCAGGGCTT	ID
								36	86-	GGCTGGTCC	NO:
									43.2	CGCTGGTGG	112
									4]	TCAG[C/T]GT
										CATTGTTGG
										CGCTGTGTG
										GGTGGACCC
										TGTGGCCTT
										GA
chr	101791	G	A	MUC6	p.T163	0.014	0.000	6.50	51.6	GGCAGAAGT	SEQ
11	2				0I	95	29	E-	5[26.	GGCCATCTG	ID
								49	44-	TGCATGGGT	NO:
									100.	AGGGGTGAT	113
									88]	GACT[G/A]TG
										TGAGTACTT
										GGAGTCACC
										AAAGAGGTG
										GAGAAAGGT
										GG
chr	101797	C	G	MUC6	p.Q16	0.007	0.000	2.56	15.7	AAGAGGTGG	SEQ
11	4				09H	60	49	E-	2[10.	AGAAAGGTG	ID
								23	08-	GAACGTGAG	NO:
									24.5	TGGGAAGTG	114
									1]	TGGT[C/G]TG
										AGGGTGTGA
										TGGGGTTGG
										ATAGGTAGT
										GGTGGTCTT
										GA
chr	102362	G	A	MUCC6	p.T113	0.009	0.007	4.58	1.4[1	GGCCTCCTG	SEQ
11	2				8M	80	03	E-	.02-	TGTGTACTG	ID
								02	1.92]	GTACTCGCC	NO:
										ATGGCCGTC	115
										CTGC[G/A]TG
										TGCGTGTTG
										TAGAAGCCG
										CAGTAGATG
										GCTGGGAGG
										AA
chr	109353	A	C	MUC2	p.K17	0.007	0.000	4.33	94.8	CACCACTAC	SEQ
11	7				86Q	11	08	E-	1[]28.	GATGACCCC	ID
								27	87-	AACCCCAAC	No:
									311.	ACCCACCAG	116
									37	CACA[A/C]AG
										AGTACAACC
										GTGACACCC
										ATCACCACC
										ACAACTACG
										GT
chr	126418	C	T	MUC5	p.T202	0.006	0.003	1.15	1.69	ACTCCAGAG	SEQ
11	7			B	6M	62	93	E-	[1.14-	ACTGCCCAC	ID
								02	2.49]	ACCTCCACA	NO:
										GTGCTTACC	117
										GCCA[C/T]GG
										CCACCACAA
										CTGGGGCCA
										CCGGCTCTG
										TGGCCACCC
										CC
chr	126996	G	A	MUC5	p.T395	0.006	0.004	4.28	1.52	CCAGTGGTA	SEQ
11	9			B	3T	86	53	E-	[1.03-	CTCCCCCAT	ID
								02	2.24]	CACTGATCA	NO:
										CCACGGCCA	118
										CTAC[G/A]AT
										CACGGCCAC
										CGGCTCCAC
										CACCAACCC
										CTCCTCAAC
										TC
chr	127131	A	G	MUC5	p.T440	0.014	0.000	2.18	Inf	CGACCTGGA	SEQ
11	3			B	1T	95	00	E-		TCCTCACAG	ID
								89		AGCTGACCA	NO:
										CAGCAGCCA	119
										CTAC[A/G]AC
										TGCAGCCAC
										TGGCCCCAC
										GGCCACCCC
										GTCCTCCAC
										CC
chr	160615	G	A	KRTA	p.G11	0.005	0.000	6.34	Inf	CACAGCCGG	SEQ
11	0			P5-1	0G	39	00	E-		AACCACAGC	ID
								31		CACCCTTGG	NO:
										ATCCCCCAC	120
										AAGA[G/A]C
										CACAGCCCC
										CCTTGGAGC
										CCCCACAGG
										AGCCACAAC
										CCC
chr	160640	G	A	KRTA	p.S26S	0.004	0.000	2.01	42.7	AGCCAGAAC	SEQ
11	2			P5-1		64	10	E-	7[16.	CTCCACAGC	ID
								11	27-	CAGAGCCAC	NO:
									112.	AGCCCCCAC	121
									48]	AGCC[G/A]G
										AGCCACAGC
										CCCCACAGC
										CGGAGCCAC
										AGCCCCCAC
										AGC
chr	161943	A	G	KRTA	p.C17	0.012	0.000	1.27	1373	AGCCCCCAC	SEQ
11	0			P5-2	C	25	01	E-	.66[1	AGCCAGAGC	ID
								71	89.7	CACAACCCC	NO:
									1-	CACAGCTGG	122
									9946	AGCC[A/G]CA
									.24]	GCCCCCACA
										GCCGGAGCC
										ACAGCCTCT
										GGAGCAGCC
										AC
chr	162916	G	A	KRTA	p.C151	0.010	0.000	5.33	1023	AGCAGGGCT	SEQ
11	3			P5-3	C	29	01	E-	.61[1	TACAGCAGC	ID
								58	40.8	TGGACTGGG	NO:
									5-	AGCAGCTGG	123
									7439	GCTT[G/A]CA
									.08]	GCAGCTGGA
										CTGGCAGCA
										GGATGACCC
										ACAGCCTGA
										GG
chr	162936	C	A	KRTA	p.K84	0.013	0.000	1.22	Inf	AGCAGCAGA	SEQ
11	4			P5-3	N	48	00	E-		CGGGCACAC	ID
								80		AGCAGCTGG	NO:
										AGCCACAGC	124
										CCCC[C/A]TT
										GGAGCCTCC
										ACAGGAGCC
										ACAGCCCCC
										CTTGCAGCC
										CC
chr	164288	A	G	KRTA	p.S148	0.011	0.000	1.28	Inf	TACAGCAGC	SEQ
11	0			P5-4	S	27	00	E-		TGGACTGGC	ID
								67		AGCAGGATG	NO:
										ACCCACAGC	125
										CTGA[A/G]GA
										GAAGCAGCA
										GGGCTTACA
										GCAGCTGCA
										CTGGGAGCA
										GC
chr	165135	A	G	KRTA	p.R97	0.027	0.000	1.04	Inf	CTGTGGCAA	SEQ
11	9			P5-5	G	94	00	E-		AGGGGGCTG	ID
								166		TGGCTCTTG	No:
										CGGGGGCTC	126
										CAAG[A/G]G
										AGGCTGTGT
										CTCCTGTGG
										GGTGTCCAA
										GGGGGCCTG
										TGG
chr	216143	G	A	IGF2	p.Q33	0.016	0.000	9.89	19.8	CGTCTAAGT	SEQ
11	0				X	68	90	E-	[11.5-	AGCTCGCCT	ID
								16	34.2]	TTGCGGCCC	No:
										ACCCAAAAT	127
										ATCT[G/A]GA
										TAATGGTTA
										CCCCGTCCT
										CAGTGCGTT
										GGACTTGCA
										TA
chr	438911	G	A	OR52B	p.T139	0.005	0.002	2.82	1.79	CAGAGAGAC	SEQ
11	0			4	I	21	91	E-	[1.01-	AGTCACACA	ID
								02	2.96]	AATTTTCTTG	No:
										ATCAGAGCA	128
										TTT[G/A]TAA
										GAATGGTGG
										TGTACCTCA
										GTGGGTAGC
										ATATGGCAA
										T
chr	544404	C	T	OR51	p.L204	0.008	0.005	1.36	1.57	CTGTGCTGA	SEQ
11	0			Q1	F	58	50	E-	[1.11-	CATCAGGCT	ID
								02	2.2]	CAACAGCTG	No:
										GTATGGATT	129
										TGCT[C/T]TT
										GCCTTGCTC
										ATTATTATC
										GTGGATCCT
										CTGCTCATT
										GT
chr	691328	T	C	OR2D	p.S151	0.008	0.004	1.80	1.67	AGTATGAAG	SEQ
11	1			2	G	133	873	E-	[1.07-	GTGGTGTCT	ID
								02	2.5]	ACCACAGAC	No:
										ACCAGAATG	130
										CCAC[T/C]GG
										TCCATGATC
										CTGTTGCCA
										GCTGGACAC
										ACACTTTCC
										AG
chr	694291	C	T	OR2D	p.S228	0.014	0.010	5.32	1.47	ATCTTTTCAA	SEQ
11	5			3	F	71	03	E-	[1.13-	TGGGCGTGG	ID
								03	1.92]	TAATCCTCCT	No:
										GGCCCCTGT	131
										CT[C/T]CCTG
										ATTCTTGGTT
										CTTATTGGA
										ATATTATCTC
										CACTGTT
chr	122463	G	A	MICAL	p.R559	0.008	0.005	2.51	1.5[1	CGCAGTGGG	SEQ
11	55			2	Q	33	56	E-	.06-	TTGGCCCTG	ID
								02	2.13]	TGTGCCATC	No:
										ATCCACCGC	132
										TTCC[G/A]GC
										CTGAGCTCA
										TGTGAGTCT
										GGGGCCCAG
										GCTGGCCCC
										TG
chr	341650	G	A	NAT10	p.A98	0.008	0.003	5.80	2.17	TGAAGAGTG	SEQ
11	53				3T	133	762	E-	[1.39-	GAATGAAGT	ID
								04	3.26]	TTTGAACAA	No:
										AGCTGGGCC	133
										GAAC[G/A]CC
										TCGATCATC
										AGCCTGAAA
										AGGTGAGGG
										CCCAGGGTC
										TG
chr	354560	T	A	PAMR	p.D53	0.007	0.005	3.47	1.49	CAAGCCCTC	SEQ
11	85			1	4V	60	11	E-	[1.04-	TCTTACCTGT	ID
								02	2.14]	AGGCTCTGG	No:
										ATGGTCTTCT	134
										CA[T/A]CCCG
										GTCATCATC
										CCGGTAGAA
										TTTCCCCAA
										AACAACTTT
chr	474696	G	T	RAPSN	p.N88	0.005	0.002	5.29	1.96	TCTTGTGAA	SEQ
11	31				K	15	63	E-	[1.26-	ACTCGCACA	ID
								03	3.06]	GCTTCTCGTT	No:
										GCTGCGTGC	135
										CAG[G/T]TTC
										AGGTAGCTC
										TCCAGGAGG
										AAGTCGGCA
										TCCTCCAGC
										T
chr	619595	A	C	SCGB1	p.N20	0.005	0.002	1.60	2.21	TCCTTACAC	SEQ
11	31			D1	T	15	33	E-	[1.42-	AAATTATAT	ID
								03	3.46]	TTTTATTCTT	No:
										TTGCTCCAG	136
										CAA[A/C]TGC
										AGTGGTCTG
										CCAAGCTCT
										TGGTTCTGA
										AATCACAGG
										C
chr	622880	G	A	AHNA	p.P462	0.007	0.004	2.38	1.54	GGACATCAA	SEQ
11	14			K	5P	60	94	E-	[1.07-	TGTCCACTTT	ID
								02	2.22]	GGGGTCCCT	No:
										GATGTCAAC	137
										TTC[G/A]GGG
										CCCTTGAGG
										TCGCCTTCC
										ACTTTGGGC
										AGAGAAATG
										T
chr	624339	C	T	METT	p.R38	0.005	0.002	2.15	1.92	ACTGGCTGA	SEQ
11	12			L12	W	21	72	E-	[1.08-	TAGTTGCCT	ID
								02	3.18]	GGCGGACCG	No:
										CTGTCTCTG	138
										GGAT[C/T]GG
										CTGCATGCC
										CAGCCTCGT
										TTGGGCACT
										GTCCCCACC
										TT
chr	624443	C	G	UBXN	p.E249	0.012	0.008	3.42	1.38	CTGAGCAAT	SEQ
11	84			1	Q	25	88	E-	[1.04-	TGCACAGGG	ID
								02	1.84]	TCCTGGCCC	No:
										CCACCTAGT	139
										TCCT[C/G]CC
										CACGGTGGA
										GCTCCACAT
										AGAGCCTCA
										CAGCTGCCA
										GC
chr	627608	C	T	SLC22	p.R422	0.005	0.003	1.35	1.75	GGCCTTTTCC	SEQ
11	00			A8	Q	88	38	E-	[1.15-	ACCTCTGGC	ID
								02	2.64]	TCCTGCTTTG	No:
										GCTTCTTTGC	140
										C[C/T]GCAGG
										GACCTAGGG
										ACAGAGAGC
										TAAGGAAAA
										GCCCTGGG
chr	634874	G	C	RTN3	p.D50	0.010	0.007	4.56	1.38	ATTGGGAGA	SEQ
11	75				1H	54	68	E-	[1.01-	AATCACAGA	ID
								02	1.87]	AGCTGATAG	No:
										TTCTGGTGA	141
										GTCT[G/C]AT
										GACACAGTA
										ATAGAGGAC
										ATCACAGCA
										GATACATCA
										TT
636815	chr	C	T	RCOR	p.T271	0.009	0.004	1.13	2.3[1	GGAGCGTGA	SEQ
11	04			2	T	31	07	E-	.65-	GGTTGGCAA	ID
								05	3.2]	GGTCCGGGC	No:
										TTCCTGACA	142
										CTGC[C/T]GT
										GAGGCCTTC
										AGGGCTCAG
										GTACATGCC
										CTTGGGTGG
										GC
chr	640518	G	A	GPR13	p.G17	0.006	0.000	6.66	48.8	CTGTGAGGA	SEQ
11	89			7	G	04	10	E-	3[20.	CAAGATGTT	ID
								15	22-	ACGTAGTCA	No:
									117.	AGGCACAGC	143
									93]	TGGG[G/A]CC
										AACGGTGGC
										CCTGGAAGG
										CAGAGGCAG
										GTACCCCTG
										GC
chr	640832	G	T	ESRRA	p.R376	0.018	0.000	4.17	28.9	GAAGCCGGC	SEQ
11	93				L	87	67	E-	[20.8	CGGGCTGGC	ID
								69	7-	CCCGGAGGG	NO:
									40]	GGTGCTGAG	144
										CGGC[G/T]GC
										GGGCGGGCA
										GGCTGCTGC
										TCACGCTAC
										CGCTCCTCC
										GC
chr	640833	G	A	ESRRA	p.A37	0.016	0.000	5.66	27.1	GCCGGGCTG	SEQ
11	00				8A	91	63	E-	7[19.	GCCCCGGAG	ID
								61	38-	GGGGTGCTG	NO:
									38.0	AGCGGCGGC	145
									8]	GGGC[G/A]G
										GCAGGCTGC
										TGCTCACGC
										TACCGCTCC
										TCCGCCAGA
										CAG
chr	649850	G	A	SLC22	p.A18	0.005	0.003	4.82	1.61	GGTCCTACC	SEQ
11	72			A20	4A	15	20	E-	[1.04-	TGCAGCTGG	ID
								02	2.51]	CAGCTTCGG	NO:
										GGGCCGCCA	146
										CAGC[G/A]TA
										TTTCAGCTCC
										TTCAGTGCC
										TATTGCGTCT
										TCCGGTTCC
chr	724060	C	T	ARAP1	p.V12	0.005	0.002	2.50	2.09	CAAGCCCAG	SEQ
11	46				251	15	47	E-	[1.34-	CGTCACCCA	ID
								03	3.25]	CCTGCCTCCT	NO:
										CCCTCTCGTT	147
										GA[C/T]CTCA
										AAGCAGGTC
										CAATAGTCC
										TTCTCCCTGA
										TGCCCACG
chr	738439	C	T	C2CD	p.R371	0.009	0.006	4.99	1.41	CAGTTGAAG	SEQ
11	93			3	R	31	62	E-	[1.02-	GGAGGAGGT	ID
								02	1.96]	GATCTTCAA	NO:
										TGTGGTCTTT	148
										AAA[C/T]CGA
										TTCCTAGAA
										AAGGCTCTG
										ATCCTAAGG
										TGTGGAAAA
										A
chr	740535	G	A	PGM2	p.T522	0.005	0.002	4.03	2.06	ATATCCAGT	SEQ
11	73			L1	I	15	51	E-	[1.32-	GGTAACGTC	ID
								03	3.21]	CCGTACATG	NO:
										CAATATAGC	149
										AAAT[G/A]TT
										CCACAAAAT
										TTTGGATATT
										CTTTTGGAG
										AATCAAAAT
										T
chr	747175	A	T	NEU3	p.X46	0.006	0.004	2.55	1.61	CCAGCCCTG	SEQ
11	37				2Y	62	13	E-	[1.09-	GTAGGAACC	ID
								02	2.37]	CAAGCCAAT	No:
										TCAAAAGCA	150
										ATTA[A/T]TT
										GGCTTAGGA
										CCCAATTTC
										CATAGATGC
										AAATGGCAG
										TT
chr	755093	C	T	DGAT	p.F247	0.012	0.000	1.70	Inf	ACTCCTTTG	SEQ
11	32			2	F	25	00	E-		GAGAGAATG	ID
								73		AAGTGTACA	No:
										AGCAGGTGA	151
										TCTT[C/T]GA
										GGAGGGCTC
										CTGGGGCCG
										ATGGGTCCA
										GAAGAAGTT
										CC
chr	755093	C	T	DGAT	p.G25	0.018	0.000	1.61	Inf	GAGAGAATG	SEQ
11	41			2	0G	14	00	E-		AAGTGTACA	ID
								108		AGCAGGTGA	No:
										TCTTCGAGG	152
										AGGG[C/T]TC
										CTGGGGCCG
										ATGGGTCCA
										GAAGAAGTT
										CCAGAAATA
										CA
chr	768348	C	A	CAPN	p.L632	0.007	0.004	9.41	1.67	GCAGCCCAG	SEQ
11	87			5	I	60	56	E-	[1.16-	CAACCTGCC	ID
								03	2.41]	AGGCACTGT	No:
										GGCCGTGCA	153
										CATT[C/A]TC
										AGCAGCACC
										TCCCTCATG
										GCTGTCTGA
										CACCTGCCC
										AC
chr	828797	C	T	PCF11	p.P795	0.007	0.005	3.85	1.47	GGACCTCCC	SEQ
11	61				L	84	34	E-	[1.03-	ACACCAGCT	ID
								02	2.11]	TCTCTTCGGT	No:
										TTGATGGGT	154
										CAC[C/T]AGG
										ACAAATGGG
										GGGAGGAGG
										CCCTTTGAG
										ATTTGAGGG
										G
chr	896073	C	T	TRIM6	p.E205	0.008	0.003	3.95	2.81	ATTCTCACTT	SEQ
11	39			4B	K	82	16	+E-	[1.96-	GACTGTCTT	ID
								07	4.02]	GTAGTTGTT	No:
										GGAAAAGCT	155
										CTT[C/T]TGC
										TTCTCTTTCC
										AGTGCCTGC
										AGATGCCGT
										TGCTCCTCC
chr	947598	G	A	KDM4	p.C381	0.008	0.003	1.56	2.17	GCTCTGGGC	SEQ
11	63			E	Y	09	74	E-	[1.5-	CTGAGGCTT	ID
								04	3.14]	CTCCCAAAC	No:
										CTCACAGCC	156
										CAGT[G/A]TC
										CCACACAGC
										CTGTGTCCTC
										AGGGCACTG
										TTACAACCC
										A
chr	961175	A	C	CCDC	p.D12	0.006	0.002	2.43	2.96	TGTTGAGAT	SEQ
11	37			82	5E	62	24	E-	[1.99-	CATTATCCTC	ID
								06	4.42]	TTGACTTAA	No:
										ATGTTTTTCC	157
										TG[A/C]TCTT
										GTAAGTCAA
										TATTCCTATG
										TTTGATTTTG
										TTCGTTT
chr	107381	G	T	ALKB	p.H47	0.006	0.004	2.37	1.63	AGAGAAAGA	SEQ
11	630			H8	4N	62	08	E-	[1.09-	AAGACCATA	ID
								02	2.43]	CTTACTGCT	No:
										GTTGCAAAA	158
										TGAT[G/T]AA
										TAACAGCAA
										TGGAGATGC
										AGGCATCAC
										AAGACCCAC
										TG
chr	114451	T	C	NXPE4	p.131V	0.005	0.003	3.81	1.62	ACAGGATTC	SEQ
11	010					39	33	E-	[1.05-	CATGTGTTTC	ID
								02	2.5]	TCCAGACAT	No:
										GCCCACTGG	159
										GGA[T/C]TGT
										GGATGTCAT
										TCCAAACTT
										GCATTTCTCT
										TTCATTGCA
chr	116744	A	G	SIK3	p.L518	0.005	0.003	3.98	1.6[1	TGTCTAGGT	SEQ
11	648				L	39	38	E-	.04-	ACCTTGTAC	ID
								02	2.46]	TCAAGTTGC	No:
										CCGGTTGGT	160
										TGCA[A/G]GT
										TTTGCATAG
										GCAACAGGT
										TGTGCATGA
										AGTTCACAT
										TA
chr	117054	G	A	SIDT2	p.R235	0.005	0.003	2.25	1.73	ATGATGATG	SEQ
11	496				H	39	13	E-	[1.12-	AAGAAGATA	ID
								02	2.66]	TTTATCATCA	No:
										TCATCCTGC	161
										AGC[G/A]CA
										AAGACTTCC
										CCAGCAACA
										GCTTTTATGT
										GGTGGTGGT
										G
chr	117057	C	T	SIDT2	p.R333	0.005	0.000	3.63	533.	ATGCAGGCA	SEQ
11	334				X	64	01	E-	81[7	GAAGAAGAA	ID
								31	2.07-	GACCCTGCT	No:
									3953	GGTGGCCAT	162
									.67]	TGAC[C/T]GA
										GCCTGCCCA
										GAAAGCGGT
										ACCTCCAGG
										GGGCCTGGG
										TG
chr	118516	G	A	PHLD	p.A11	0.005	0.002	2.98	2.47	CCTGCCTGC	SEQ
11	274			B1	08T	39	19	E-	[1.59-	GGGGCGGGA	ID
								04	3.82]	GCGTGGGGA	No:
										GGAGGGTGA	163
										GCAC[G/A]CC
										TATGATACG
										CTGAGTCTG
										GAGAGCTCT
										GACAGCATG
										GA
chr	118850	C	G	FOXR	p.A15	0.005	0.000	7.54	287.	GACAGCTCC	SEQ
11	225			1	3G	15	02	E-	7[67.	TCTATGGCT	ID
								29	44-	CTCCCATCC	No:
									1227	CCTCACAAA	164
									.4]	AGGG[C/G]CC
										CCCTCCAGA
										GTCGGAGGC
										TTCGGCAAG
										CCAGCAGCC
										AG
chr	120188	T	A	POU2	p.F422	0.018	0.000	5.03	2148	TCAAAATAA	SEQ
11	060			F3	I	87	01	E-	.21[2	CTCCAAAGC	ID
								111	98.7	AGCAGTGAA	No:
									1-	CTCCGCCTC	165
									1544	CAGT[T/A]TT
									8.8]	AACTCTTCA
										GGGTAAGGT
										GAAGGGGAC
										GGTGCAGAG
										AC
chr	123476	C	T	GRAM	p.A29	0.006	0.003	8.40	1.76	TCACCAACA	SEQ
11	177			D1B	5A	37	64	E-	[1.18-	GCACACTAA	ID
								03	2.62]	CATCCACAG	No:
										GGAGCAGTG	166
										AGGC[C/T]CC
										CGTCTCGGT
										ATGGGCAGT
										CAGCCTTTG
										ACTTCTACC
										CC
chr	124266	A	G	OR8B3	p.P286	0.009	0.003	1.44	3.04	GTGCAACTT	SEQ
11	390				P	31	09	E-	[2.17-	TGACATCCT	ID
								08	4.25]	TGTTCCTCA	No:
										AACTGTAGA	167
										TGAG[A/G]G
										GATTGAGCA
										TGGGCACCA
										CATTAGTGT
										AGAAAACAG
										AAG
chr	124620	G	T	VSIG2	p.N97	0.005	0.000	6.91	288.	CGTCAGTCA	SEQ
11	746				K	15	02	E-	96[6	GTTTCAGTG	ID
								29	7.73-	TGGCCACCC	No:
									1232	CCACTGTGG	168
									.76]	GGGG[G/T]TT
										CTGAAGCAG
										GCTGACCCG
										CTTTGACTTA
										GAACCAGTT
										G
chr	368928	T	C	SLC6A	p.P97P	0.008	0.005	2.84	1.72	CCTCTAAGC	SEQ
12				13		8 2	15	E-	[1.23-	GTCCTCCTA	ID
								03	2.41]	CCTCCAGAA	No:
										TTCTATACAT	169
										CTA[T/C]GGG
										ACTCCCCAG
										AGGGGCCGT
										AAGTGCAGG
										AGATGGAAG
										T
chr	704483	C	T	ATN1	p.Y13	0.011	0.007	1.73	1.46	ATATCGACC	SEQ
12	8				6Y	03	57	E-	[1.08-	AGGACAACC	ID
								02	1.98]	GAAGCACGT	No:
										CCCCCAGTA	170
										TCTA[C/T]AG
										CCCTGGAAG
										TGTGGAGAA
										TGACTCTGA
										CTCATCTTCT
										G
chr	109594	C	A	TAS2R	p.R55I	0.007	0.004	1.11	1.65	TACAATGCC	SEQ
12	16			8		84	77	E-	[1.15-	ATTTACAAC	ID
								02	2.36]	CATTACACT	No:
										GATCAAACA	171
										AATT[C/A]TG
										GCGATAACT
										AAATTGGTA
										AGGATGTAG
										TCAACTGTG
										GA
chr	114617	G	T	PRB4	p.P50T	0.026	0.006	4.29	3.98	TGTGGGGGT	SEQ
12	69					72	86	E-	[3.23-	GGTCCTTGT	ID
								29	4.9]	GGCTTTCCT	No:
										GGAGGAGGT	172
										GGGG[G/T]AC
										GTTGGGGCT
										GGTTTCCTCC
										TTGTGGGCG
										TCGTCCTTCT
chr	130615	A	G	GPRC	p.I134	0.013	0.009	1.04	1.45	CAAGCTCGT	SEQ
12	83			5A	V	48	32	E-	[1.11-	CCGGGGGAG	ID
								02	1.91]	GAAGCCCCT	No:
										TTCCCTGTTG	173
										GTG[A/G]TTC
										TGGGTCTGG
										CCGTGGGCT
										TCAGCCTAG
										TCCAGGATG
										T
chr	152623	C	T	RERG	p.V95	0.009	0.006	1.84	1.49	TGGGCTTTTT	SEQ
12	59				V	80	58	E-	[1.09-	GATCTCATC	ID
								02	2.06]	TAGGATGTT	NO:
										CTTAAGTGG	174
										CAG[C/T]ACT
										TCCTCAAAA
										CTTCCTCGGT
										CAGTAATGT
										CGTAGACCA
chr	482402	G	A	VDR	p.A35	0.005	0.003	1.83	1.71	GGAACTTGA	SEQ
12	33				3A	64	30	E-	[1.11-	TGAGGGGCT	ID
								02	2.64]	CAATCAGCT	NO:
										CCAGGCTGT	175
										GTCC[G/A]GC
										TGTGAGAGA
										CAATGGCCA
										GGTACTGCG
										GGCAGAGCT
										GA
chr	494255	C	T	KMT2	p.V43	0.005	0.002	1.83	2.1[1	TTTGGCTCTT	SEQ
12	75			D	05I	39	57	E-	.36-	GAGGGCTGG	ID
								03	3.25]	ATGGTGGAG	NO:
										GTGTGGGAT	176
										GGA[C/T]AGG
										GCCAAGGAC
										TGGTCCTGT
										AGATAAGGC
										TCCTGGTGG
										G
chr	504801	G	T	SMAR	p.Q11	0.007	0.004	8.42	1.8[1	CCCGCAAGA	SEQ
12	02			CD1	2H	807	359	E-	.14-	GACCTGCCC	ID
								03	2.71]	CTCAGCAGA	NO:
										TCCAGCAGG	177
										TCCA[G/T]CA
										GCAGGCGGT
										CCAAAATCG
										AAACCACAA
										GTAAGATGA
										TC
chr	507457	G	A	FAM1	p.A16	0.005	0.000	3.41	10.5	CTGGGCCTG	SEQ
12	92			86A	08V	88	56	E-	6[6.1	CTGAGGGGT	ID
								14	9-	GAGAGGGAT	NO:
									18.0	CCCCTGAGC	178
									2]	CTGC[G/A]CC
										TGCTGAGGG
										GTGAGAGGG
										ATCCCCAGT
										TCCTGCGCC
										TG
chr	507468	A	G	FAM1	p.V12	0.025	0.000	7.89	399.	CTGGGCCTG	SEQ
12	36			86A	60A	74	07	E-	44[1	CTGAGGAGT	ID
								110	26.7	AAGAGGGAT	NO:
									2-	CCCCAGTTC	179
									1259	CTGA[A/G]CC
									.11]	TGCTTAGGG
										GTGAGAGTG
										ATTCCGAGA
										GCCTGCGCC
										TG
chr	507481	T	G	FAM1	p.K81	0.005	0.002	1.29	1.97	TCTTGCAAA	SEQ
12	69			86A	6Q	21	65	E-	[1.11-	TATTGCTCCT	ID
								02	3.26]	GCCTTTGTTT	No:
										TTCCTTCTCC	180
										T[T/G]GTGGT
										CTTTCTGTAC
										TGTTGAGAC
										TGTTGGAAT
										ATCTCTT
chr	529608	C	A	KRT74	p.G50	0.005	0.002	9.47	2.09	GGCTGGGGT	SEQ
12	23				7V	21	49	E-	[1.18-	GCTCTTGCC	ID
								03	3.47]	CTGGGTGTC	No:
										CTTGAGGTC	181
										TCCC[C/A]CT
										CGCGCCTCT
										GTGGTCTTG
										GTCTGCCCG
										CTCTGGGTG
										CT
chr	529620	G	A	KRT74	p.R420	0.008	0.005	2.50	1.51	AGTTTCAGG	SEQ
12	50				W	33	55	E-	[1.06-	CTCATGAGC	ID
								02	2.13]	TCCTGGTAC	No:
										TCGCGCAGC	182
										ATCC[G/A]CG
										CCAGCTCCT
										CCTTGGCCT
										GGTGCAGGG
										CGCCCTCCA
										GC
chr	534481	G	A	TENC1	p.T13	0.005	0.003	1.35	1.79	TCATGGAGC	SEQ
12	14				T	39	01	E-	[1.16-	GGCGCTGGG	ID
								02	2.77]	ACTTAGACC	No:
										TCACCTACG	183
										TGAC[G/A]GA
										GCGCATCTT
										GGCCGCCGC
										CTTCCCCGC
										GCGGCCCGA
										TG
chr	535169	C	T	SOAT2	p.V45	0.010	0.007	2.52	1.45	TGGGGTTCT	SEQ
12	93				5V	54	32	E-	[1.06-	TCTATCCCGT	ID
								02	1.97]	CATGCTGAT	No:
										ACTCTTCCTT	184
										GT[C/T]ATTG
										GAGGTGAGC
										TGGTCTCTGT
										GCCACTGGA
										AGGGAGCC
chr	537144	G	T	AAAS	p.T57	0.009	0.000	5.15	Inf	GATGAAGGC	SEQ
12	30				N	31	00	E-		AGTTCTTGT	ID
								56		GCCATGGTC	No:
										CAGCCTTCC	185
										AGGG[G/T]TC
										TTTAGGGGA
										TCCTTTGTCA
										GTTGTAGGA
										CAGGAAGAT
										T
chr	558464	C	A	OR6C2	p.L164	0.005	0.002	1.70	1.8[1	TGATGATCA	SEQ
12	89				L	15	87	E-	.16-	TTGTTCCACC	ID
								02	2.8]	ACTTAGCTT	No:
										AGGCCTCCA	186
										GCT[C/A]GAA
										TTCTGTGACT
										CCAATGCCA
										TTGATCATTT
										TAGCTGTG
chr	563509	C	G	PMEL	p.E370	0.005	0.002	5.00	2.3[1	CCTCTGAAA	SEQ
12	77				D	88	57	E-	.51-	CTGGCACCT	ID
								04	3.49]	TCTCAGGTG	No:
										TCATACCTG	187
										TGCT[C/G]TC
										TGCAGTTGG
										CATCTGCAC
										AGGTGCAGT
										GCTTATGAC
										TT
chr	570092	G	A	BAZ2A	p.N10	0.007	0.004	4.23	1.48	GTCCCCCCG	SEQ
12	16				6N	35	97	E-	[1.02-	AGAACTGGG	ID
								02	2.14]	AGAGAAGGG	No:
										GTGGGTCCT	188
										TGAG[G/A]TT
										GCTGCCAGG
										ATTGGCAGA
										TGGGTACTG
										TGAGTAGTT
										CC
chr	575693	G	A	LRP1	p.G12	0.008	0.005	8.35	1.64	GAAGGCATT	SEQ
12	39				15E	58	26	E-	[1.16-	GTGTGTTCCT	ID
								03	2.3]	GCCCTCTGG	No:
										GCATGGAGC	189
										TGG[G/A]GCC
										CGACAACCA
										CACCTGCCA
										GATCCAGAG
										CTACTGTGC
										C
chr	667251	G	A	HELB	p.G95	0.005	0.003	2.31	1.66	TCGTTTGAA	SEQ
12	38				9S	88	56	E-	[1.1-	ACATTTCTTG	ID
								02	2.51]	CAAAGTAAG	No:
										CTCTCCTCTA	190
										GC[G/A]GCGC
										ACCTCCAGC
										AGATTTTCC
										GTCCCCACG
										GAAGAGCTC
chr	856951	C	T	ALX1	p.N27	0.009	0.000	1.86	Inf	TTTCAAACC	SEQ
12	06				8N	56	00	E-		ACCAGAACC	ID
								57		AGTTCAGCC	No:
										ACGTGCCCC	191
										TCAA[C/T]AA
										TTTTTTCACT
										GACTCTCTTC
										TTACTGGGG
										CAACCAATG
chr	899169	G	A	POC1	p.I450I	0.006	0.004	3.83	1.55	GGTTGTTGT	SEQ
12	68			B-		62	28	E-	[1.05-	CAGGAGAAT	ID
				GALN				02	2.29]	TATAATCTA	No:
				T4						AACATTCAG	192
										ACGA[G/A]AT
										CCCTCTACT
										GCGAATAGC
										CCCATGCCA
										GCCTGGTCT
										AT
chr	956942	C	T	VEZT	p.P712	0.001	0.000	1.23	41.5	TGAACCACA	SEQ
12	43				S	96	05	E-	[11.7-	AGCAGATGG	ID
								05	147]	AAGTGGTCT	No:
										GACCACTGC	193
										CCCT[C/T]CA
										ACTCCCAGG
										GACTCATTA
										CAGCCCTCC
										ATTAAGCAG
										AG
chr	104144	C	T	STAB2	p.P217	0.006	0.003	1.77	1.68	CTATGTCGG	SEQ
12	426				0S	13	66	E-	[1.12-	AGATGGGCT	ID
								02	2.52]	GAACTGTGA	No:
										GCCGGAGCA	194
										GCTG[C/T]CC
										ATTGACCGC
										TGCTTACAG
										GACAATGGG
										CAGTGCCAT
										GC
chr	108920	G	A	SART3	p.D69	0.005	0.003	3.10	1.62	TGATGCTGT	SEQ
12	173				1D	64	48	E-	[1.06-	CCTTGCTGCT	ID
								02	2.47]	GTCGTGCAG	No:
										CACCTTGGG	195
										CAT[G/A]TCC
										CTCTTCAGG
										GAGGCTGCC
										TTCTCCTTCT
										GCTTCGAAG
chr	111317	T	C	CCDC	p.L172	0.007	0.004	4.98	1.49	CTCCAGCAC	SEQ
12	855			63	S	11	78	E-	[1.03-	TGCCTGTTG	ID
								02	2.17]	ATGGAGAAG	No:
										AAAACCATG	196
										AACT[T/C]GG
										CCATTGAGC
										AATCTTCTC
										AGGCCTATG
										AGCAGAGGT
										GG
chr	119594	C	T	SRRA1	p.5529	0.013	0.000	4.82	Inf	CCATCCCCT	SEQ
12	354			4	S	48	00	E-		ACTATCGGC	ID
								80		CCAGCCCCT	No:
										CCTCATCCG	197
										GCAG[C/T]CT
										CAGCAGCAC
										CTCCTCCTG
										GTACAGCAG
										CAGCAGTAG
										CC
chr	122361	C	T	WDR6	p.R188	0.012	0.008	5.94	1.53	TGAAAGGCA	SEQ
12	711			6	W	25	07	E-	[1.15-	GCCCTCAGG	ID
								03	2.03]	AGAGCTTGA	No:
										GGAGAAAAC	198
										CGAC[C/T]GG
										ATGCCCCAA
										GATGAACTG
										GGACAAGAA
										AGAAGGGAC
										TT
chr	122404	C	T	WDR6	p.R860	0.012	0.008	1.00	1.49	ACAAGTCCT	SEQ
12	946			6	C	01	07	E-	[1.12-	CCCAGTGAG	ID
								02	1.99]	AAGCATGGC	No:
										GGAGCTACA	199
										GAAA[C/T]GC
										TACTTGGTG
										TTTATTAAC
										AGAGACAAG
										GTAACAGCG
										CT
chr	122676	A	G	LRRC4	p.Y15	0.005	0.002	3.52	2.01	CCCGAAGGC	SEQ
12	056			3	9C	39	69	E-	[1.3-	CCTTTCATCA	ID
								03	3.1]	CTTACAACT	No:
										ATTACGTGA	200
										CCT[A/G]TGA
										TTTTGTGAA
										AGATGAAGA
										AGGCGAAAT
										GAATGAGTC
										C
chr	123706	T	G	MPHI	p.S160	0.006	0.000	8.30	14.3	GTGGATTCA	SEQ
12	313			SPH9	R	51	46	E-	6[7.8-	GGATAATGG	ID
								15	25.7	ATAACAGAT	No:
									8]	TCATTTCTCT	201
										CAC[T/G]GCT
										TAGAGAAAA
										AAAACCCAT
										TTGACTTTCC
										GAAGATACT
chr	124364	C	T	DNAH	p.H27	0.007	0.004	1.93	1.59	GGGATCCCA	SEQ
12	285			10	39H	35	64	E-	[1.1-	TATTGTTTGG	ID
								02	2.3]	AGACTTCCA	No:
										GATGGCTCT	202
										GCA[C/T]GAA
										GGAGAACCA
										CGCATTTAT
										GAAGACATC
										CAGGACTAC
										G
chr	125396	G	A	UBC	p.D49	0.028	0.012	4.07	2.27	CATCTTCCA	SEQ
12	833				5D	92	95	E-	[1.69-	GCTGTTTCCC	ID
								08	3.06]	AGCAAAGAT	No:
										CAACCTCTG	203
										CTG[G/A]TCA
										GGAGGGATG
										CCTTCCTTGT
										CTTGGATCTT
										TGCCTTGA
chr	125397	T	C	UBC	p.Q25	0.005	0.000	1.03	71.9	AGATCAACC	SEQ
12	541				9Q	15	07	E-	8[31.	TCTGCTGGT	ID
								24	86-	CAGGAGGAA	NO:
									162.	TGCCTTCCTT	204
									59]	GTC[T/C]TGG
										ATCTTTGCTT
										TGACGTTCT
										CGATAGTGT
										CACTGGGCT
chr	125398	A	G	UBC	p.T7T	0.012	0.000	1.46	94.0	CACTGGGCT	SEQ
12	297					53	10	E-	3[44.	CAACCTCGA	ID
								33	17-	GGGTGATGG	NO:
									200.	TCTTACCAG	205
									19]	TCAG[A/G]GT
										CTTCACGAA
										GATCTGCAT
										TGTCTAACA
										AAAAAGCCA
										AA
chr	132625	G	A	DDX5	p.S487	0.022	0.000	2.59	2540	CCAGGACCA	SEQ
12	260			1	S	30	01	E-	.86[3	GGTGCAGGA	ID
								131	54-	CGACCAGCG	NO:
									1823	GCTTAGAGC	206
									7.12]	TGAG[G/A]CT
										GCAGGGCAC
										GTAGTGGTG
										CTACAGGGA
										CGGCAGGGG
										GT
chr	368717	G	T	CCDC	p.V25	0.006	0.003	1.29	1.72	GGGACCCCA	SEQ
13	82			169	V	37	72	E-	[1.14-	CACCGCGCC	ID
								02	2.59]	GCCCGCCGA	NO:
										CTCACTTCTT	207
										GCG[G/T]ACT
										TCTTCCAGC
										AACTGCTGT
										TTCAGGCGG
										TTGGTGCTC
										A
chr	423521	T	C	VWA8	p.M76	0.005	0.003	2.56	1.62	ACCAATAAT	SEQ
13	71				7V	88	63	E-	[1.07-	AAGTGTTCT	ID
								02	2.45]	CCAAGGAGA	NO:
										AAGTCTTTC	208
										AGCA[T/C]AT
										CTTCCATCA
										CTATCACAT
										GCTAGAGAA
										AAAGGAACT
										AG
chr	492817	T	A	CYSLT	p.L278	0.016	0.001	1.09	10.3	CACACTGAG	SEQ
13	85			R2	I	93	66	E-	7[7.3	GACCGTCCA	ID
								30	2-	CTTGACGAC	NO:
									14.5]	ATGGAAAGT	209
										GGGT[T/A]TA
										TGCAAAGAC
										AGACTGCAT
										AAAGCTTTG
										GTTATCACA
										CT
chr	763816	T	C	LMO7	p.H18	0.008	0.004	7.04	1.9[1	TCCAAACAT	SEQ
13	79				7H	82	66	E-	.36-	ACTCTGATG	ID
								04	2.67]	ACATCTTGT	No:
										CTTCTGAAA	210
										CACA[T/C]AC
										CAAAATTGA
										TCCCACTTCT
										GGCCCAAGG
										CTCATAACC
										C
chr	995404	G	T	DOCK	p.P679	0.008	0.000	3.06	Inf	CGTAGGTGA	SEQ
13	20			9	T	33	00	E-		ACATATATT	ID
								49		AAAAAAAAA	No:
										CAAACCTTA	211
										AGGG[G/T]CT
										GAGAGTCTT
										CCTCATCTG
										AATCTTTGA
										ATTCAATGC
										AA
chr	103382	T	C	CCDC	p.K69	0.000	0.000	1.26	14.3	TTTTCTTTCA	SEQ
13	057			168	97R	25	02	E-	1[0.8	GAATAGAAG	ID
								01	9-	TTGATATCG	No:
									228.	TCATGATGA	212
									77]	GGT[T/C]TTG
										ATGCTGATT
										TATGTTTGCT
										TTGGAAACA
										ATCCAATCT
chr	103382	G	A	CCDC	p.T685	0.000	0.000	2.60	2.18	TCTATATTTC	SEQ
13	483			168	5I	49	22	E-	[0.49-	CTGCTTTTGT	ID
								01	9.67]	GGGACTTAC	No:
										AGGAAGGTG	213
										GT[G/A]TAAT
										AATTAAGGT
										TTCCTTTCTG
										CACTCTCTA
										GTACAATG
chr	103382	A	G	CCDC	p.V67	0.009	0.008	4.27	1.13	TTCTGATTCC	SEQ
13	660			168	96A	56	43	E-	[0.82-	TGACTTAAA	ID
								01	1.57]	TAAGAGTTG	No:
										GCTTCCAGA	214
										AAC[A/G]CAC
										ATTCCTCACT
										CTCACTTACT
										TCAAGACAT
										GAACACTC
chr	103382	C	T	CCDC	p.E678	0.000	0.000	2.43	4.63	ACACATTCC	SEQ
13	700			168	3K	25	05	E-	[0.48-	TCACTCTCA	ID
								01	44.5	CTTACTTCA	No:
									2]	AGACATGAA	215
										CACT[C/T]GT
										CCAAGTCAG
										CTGGACTCT
										CAATATCTG
										TCTGAATAT
										CA
chr	103383	C	T	CCDC	p.E660	0.000	0.000	1.87	7[0.6	TATTGTAAA	SEQ
13	228			168	7K	25	04	E-	3-	TCAAGATCT	ID
								01	77.2	ATTTGATGG	No:
									1]	AGAGATTTC	216
										TCCT[C/T]AG
										AAAGTAACA
										AAATTCTGT
										TTTGTCGTTT
										TGGTCCTGT
										G
chr	103383	T	C	CCDC	p.R657	0.000	0.000	2.19	2.5[0	TTCTTTCTCT	SEQ
13	339			168	0G	49	20	E-	.55-	CATGAGCAC	ID
								01	11.2	TGGTCATTG	No:
									7]	CATAAGATT	217
										CTC[T/C]TAC
										AATTCTGGG
										AAAGGCTTT
										CATTTGTATC
										TCCAATGTT
chr	103383	T	G	CCDC	p.E650	0.002	0.002	1.00	0.96	ATTTTCTAGC	SEQ
13	524			168	8A	70	81	E+0	[0.52-	TTATTAATA	ID
								0	1.77]	CTCTGTAGC	No:
										TTTGTGATTG	218
										TC[T/G]CCTC
										ACTGTCACT
										TGAAACATC
										AACAATCAG
										TGTCTTCAT
chr	103383	A	C	CCDC	p.S646	0.000	0.000	1.89	6.91	GTCCCTTCTA	SEQ
13	666			168	1A	25	04	E-	[0.63-	GAGACATAA	ID
								01	76.1	AGTTCATTG	No:
									9]	TTTTATGTCT	219
										AG[A/C]ATAG
										AACCTCCAA
										CTGTTATCTT
										TTGAAATAG
										TCCCTTTT
chr	103383	G	A	CCDC	p.H64	0.002	0.000	1.49	9.81	ATCAGATTC	SEQ
13	792			168	19Y	94	30	E-	[4.68-	AGTTGTATTT	ID
								07	20.5	CAAGTGCTT	No:
									6]	TTGACTCTA	220
										AAT[G/A]ACT
										AGTAAGCTT
										ATTTTTTTCT
										TTGGGAGTA
										AACTGTTCT
chr	103383	T	G	CCDC	p.E641	0.000	0.000	6.73	Inf	AAGTGCTTT	SEQ
13	812			168	2A	25	00	E-	[NaN-	TGACTCTAA	ID
								02	Inf]	ATGACTAGT	No:
										AAGCTTATT	221
										TTTT[T/G]CT
										TTGGGAGTA
										AACTGTTCT
										AAAAGGGAT
										TTGTGCTGC
										GT
chr	103383	C	T	CCDC	p.D63	0.001	0.002	2.75	0.61	AAGTCGTCA	SEQ
13	951			168	66N	72	82	E-	[0.28-	GGCTTATAG	ID
								01	1.3]	GCTTGTATG	NO:
										TTATCTAGTT	222
										TAT[C/T]AGA
										AGAAACTTT
										GTCTTGGAT
										CATATTTTTA
										ACCTGGGAC
chr	103384	C	T	CCDC	p.S632	0.000	0.000	4.28	1.98	ATGTTCTGC	SEQ
13	070			168	6N	25	12	E-	[0.24-	ATTTGTACT	ID
								01	16.0	GTCTGCAAC	No:
									6]	TATTTTGACT	223
										TCG[C/T]TAC
										TTTTAACTTG
										AGGCGGTAT
										GGGCACAGT
										TCCTGGGAA
chr	103384	G	A	CCDC	p.T611	0.021	0.024	1.58	0.85	ATACTCTAA	SEQ
13	712			168	2M	32	94	E-	[0.68-	TTTCTTTCTA	ID
								01	1.06]	TTGCTTGGT	NO:
										GTACCACGC	224
										CCC[G/A]TGA
										TATTAAGCA
										TCTGTGGAA
										TTGGGTGAT
										TCTGGATTTT
chr	103385	T	C	CCDC	p.K59	0.003	0.004	5.30	0.81	GGGTGTGCA	SEQ
13	064			168	95E	43	24	E-	[0.47-	CTACTGCTT	ID
								01	1.39]	GTGTCCATT	NO:
										CTTCCTCTCT	225
										CCT[T/C]CTC
										CAGATTGGC
										AGTCCTGGC
										CTTGTGCAT
										CTCTGTTTTC
chr	103385	G	A	CCDC	p.P591	0.000	0.000	6.72	Inf	TGATTGAAA	SEQ
13	294			168	8L	25	00	E-	[NaN-	TTGAAAAGT	ID
								02	Inf]	CCAGGGAGG	NO:
										GAATAGGGA	226
										CTTC[G/A]GA
										AGAAATTCC
										AGAACACCT
										TCCTCTTGTT
										CTGAAATGA
										G
chr	103385	C	A	CCDC	p.A59	0.000	0.000	4.26	1.99	AATTCCAGA	SEQ
13	340			168	03S	25	12	E-	[0.24-	ACACCTTCC	ID
								01	16.1	TCTTGTTCTG	No:
									6]	AAATGAGCA	227
										ATG[C/A]CTG
										CTTCCTTCCC
										CCTTTTGCA
										GGGTCAATC
										TCTGTCATA
chr	103385	C	T	CCDC	p.G58	0.000	0.000	1.31	13.7	GGAAACTTA	SEQ
13	520			168	43R	25	02	E-	5[0.8	GAAAGGATA	ID
								01	6-	GTGTTCGTC	NO:
									219.	CTGGTCTTGT	228
									86]	GCC[C/T]ATG
										TTCACACCG
										TCGGATCAC
										TTGCTTTTTC
										ATGACAATA
chr	103385	G	T	CCDC	p.S579	0.000	0.000	1.00	0.86	TTTGAGTGA	SEQ
13	654			168	8Y	25	28	E+0	[0.11-	TCCCTTTGTC	ID
								0	6.5]	TGTGGTGCT	NO:
										AACACTTTG	229
										GGA[G/T]AA
										AACATTTTG
										CTGATTCTAT
										CATTACTTTG
										TCCATCTTC
chr	103386	C	T	CCDC	p.V56	0.000	0.000	6.74	Inf	GCCTCTGGG	SEQ
13	222			168	09I	25	00	E-	[NaN-	CGGGGCACA	ID
								02	Inf]	TACTGTTCTG	NO:
										CTTGCTTAA	230
										CAA[C/T]GTT
										TTTATCAAC
										GCCTTCAAC
										TGAGTCTCT
										ATTTGTTATT
chr	103387	C	T	CCDC	p.V53	0.000	0.000	2.98	3.42	TGCTTTTCAT	SEQ
13	002			168	49I	25	07	E-	[0.38-	TTTTAACATC	ID
								01	30.5	TTTTGGGAT	NO:
									6]	ATCACCAAC	231
										GA[C/T]GGAC
										TCTCTATGTA
										CAGTCTCCC
										CTATGTGTG
										ATATTCTC
chr	103387	C	T	CCDC	p.R533	0.002	0.004	1.64	0.63	GGACTCTCT	SEQ
13	043			168	5Q	70	28	E-	[0.34-	ATGTACAGT	ID
								01	1.15]	CTCCCCTAT	NO:
										GTGTGATAT	232
										TCTC[C/T]GC
										AAAATAGGT
										CTTTTAAGTC
										TTAGCATTTC
										ATTACCTAA
chr	103387	G	A	CCDC	p.P528	0.020	0.017	2.99	1.13	TTCACCTTCA	SEQ
13	196			168	4L	10	80	E-	[0.9-	CATTCCTGC	ID
								01	1.42]	ACCTTCTCTT	NO:
										CCTGATGTTT	233
										G[G/A]GGAA
										TATTAAGAT
										GCTTACTATT
										TGCACGTCA
										TCCTCTTC
chr	103387	C	A	CCDC	p.G52	0.000	0.000	4.64	Inf	GATTAAAAT	SEQ
13	313			168	45V	49	00	E-	[NaN-	ATCACCAGC	ID
								03	Inf]	AATTGGCCT	No:
										TATACATGT	234
										GCCT[C/A]CC
										TCAGTATCT
										GGTGATACC
										TGGAGTTTT
										ACTAGGGGA
										AA
chr	103387	C	T	CCDC	p.V50	0.000	0.000	5.68	6.92	GACCGTGAC	SEQ
13	767			168	94M	49	07	E-	[1.27-	TGTGGGAGA	ID
								02	37.8	GACACTTTT	No:
									1]	GCAATTCTT	235
										ATCA[C/T]GT
										TCTCCTGTCC
										TTCTGTTGTA
										TCAAACTTA
										AGATATGGT
chr	103388	C	G	CCDC	p.G50	0.035	0.034	7.24	1.03	TTTGTCTTCC	SEQ
13	015			168	11A	78	78	E-	[0.87-	ATATCTATTC	ID
								01	1.22]	TGAGTCCAC	No:
										CTTTCTCTTC	236
										T[C/G]CCTGT
										GCTGTGGGT
										TGCACTGGT
										CCTTTTGAGT
										TGCTTAA
chr	103388	A	T	CCDC	p.L490	0.000	0.000	1.30	13.8	CCATTGCAT	SEQ
13	343			168	2M	25	02	E-	3[0.8	AGAAGTGCA	ID
								01	7-	AGTGGGAGT	No:
									221.	GCCTCTGCC	237
									2]	CTCA[A/T]AT
										GTATCCTTTT
										GGGGAGTAT
										TCTACCTTCC
										CTGCCTTCT
chr	103388	C	T	CCDC	p.G48	0.002	0.003	3.31	0.7[0	CCTCAAATG	SEQ
13	378			168	90D	45	50	E-	.37-	TATCCTTTTG	ID
								01	1.32]	GGGAGTATT	No:
										CTACCTTCCC	238
										TG[C/T]CTTC
										TATTTTTACT
										CTGTCCTTTG
										CCTCTTTATA
										TGGCAT
chr	103388	G	A	CCDC	p.P472	0.002	0.003	6.78	0.85	GTTTGCCTTG	SEQ
13	877			168	4S	94	48	E-	[0.47-	AAGGCAATG	ID
								01	1.52]	ATTCCTGGA	No:
										TCTCAAGAT	239
										GTG[G/A]CAT
										AAAGCTTCT
										TGTTATTCGT
										GGTTCACCT
										TCCTCTTCT
chr	103388	T	C	CCDC	p.M47	0.043	0.041	5.14	1.05	TGCCTTGAA	SEQ
13	880			168	23V	14	03	E-	[0.9-	GGCAATGAT	ID
								01	1.23]	TCCTGGATC	NO:
										TCAAGATGT	240
										GGCA[T/C]AA
										AGCTTCTTGT
										TATTCGTGG
										TTCACCTTCC
										TCTTCTTTT
chr	103389	G	A	CCDC	p.P465	0.001	0.000	6.03	7.86	TTCACCTGC	SEQ
13	072			168	9S	96	25	E-	[3.3-	AGTTCCTTTG	ID
								05	18.7	TTTTTAGTAT	No:
									51]	ATGGGAAAG	241
										GG[G/A]TGAT
										TTCTCTGCCT
										TTACAGCTA
										TGTACTCGG
										GATGCATT
chr	103389	T	G	CCDC	p.K46	0.004	0.002	6.72	1.6[0	TGAAATATT	SEQ
13	164			168	28T	41	76	E-	.98-	TGCTTTATCC	ID
								02	2.61]	TTTTGGATCT	NO:
										GGGCCATGT	242
										AT[T/G]TTGT
										TCTGTTTGA
										ATCACCTGT
										GATATCATT
										CAAATATGA
chr	103389	G	A	CCDC	p.R458	0.000	0.000	2.68	2.13	GATCTTGTT	SEQ
13	306			168	1X	49	23	E-	[0.48-	ACTCCTTGTT	ID
								01	9.44]	CCTCTTTTTT	NO:
										GCCTGCTGT	243
										TC[G/A]TTTG
										TCTAATTTAC
										AGTGAGATA
										GAGAAGGTA
										TTGTCAGA
chr	103389	A	G	CCDC	p.C457	0.000	0.000	3.09	9.25	TGTTCCTCTT	SEQ
13	321			168	6R	98	11	E-	[2.61-	TTTTGCCTGC	ID
								03	32.7	TGTTCGTTTG	NO:
									9]	TCTAATTTAC	244
										[A/G]GTGAG
										ATAGAGAAG
										GTATTGTCA
										GAAACACAT
										CCAGTTCA
chr	103389	C	A	CCDC	p.V44	0.000	0.000	1.89	6.93	TTGTATTCTT	SEQ
13	594			168	85L	25	04	E-	[0.63-	GTACTGTTTT	ID
								01	76.4]	TACATCATTT	NO:
										GAGCTATCC	245
										A[C/A]CCCAA
										AAGACTTTG
										TATGTGCTA
										TTTTCCCTGC
										ATCAAAT
chr	103389	A	G	CCDC	p.L446	0.002	0.001	8.43	1.8[0	TATTTTCCCT	SEQ
13	656			168	4S	45	36	E-	.93-	GCATCAAAT	ID
								02	3.48]	GATTTCTGCT	No:
										GCCTTAGTT	246
										GC[A/G]AAGT
										AGCAGATTT
										TATTATTCCT
										TGTAAGTCT
										TCCTCTCC
chr	103389	C	T	CCDC	p.E439	0.000	0.000	1.30	13.8	TGTTGCTCTT	SEQ
13	867			168	4K	25	02	E-	7[0.8	CAGTTTCTCC	ID
								01	7-	ATCCCTGTTC	No:
									221.	CCTTGCTCCT	247
									8]	[C/T]ACCTTC
										TCCGTCCTCT
										TTCCCTTGCT
										CCTGGCCTT
										CTCCA
chr	103389	T	G	CCDC	p.K43	0.011	0.014	7.81	0.76	CCATCCCTG	SEQ
13	885			168	88Q	27	80	E-	[0.56-	TTCCCTTGCT	ID
								02	1.02]	CCTCACCTTC	No:
										TCCGTCCTCT	248
										T[T/G]CCCTT
										GCTCCTGGC
										CTTCTCCATC
										CCTTTTCCCT
										GGCTCT
chr	103390	C	T	CCDC	p.G43	0.004	0.003	2.99	1.27	ATGTAATCT	SEQ
13	083			168	22S	90	86	E-	[0.8-	TTTGCTTTTT	ID
								01	2.01]	GTACTTCAC	No:
										TTGCGCTAT	249
										CAC[C/T]CTC
										ACTGGGCAC
										CCCATTTGCT
										TTTTTCCCTG
										TCTCTGAT
chr	103390	C	T	CCDC	p.E432	0.012	0.010	2.45	1.19	TAATCTTTTG	SEQ
13	086			168	1K	99	98	E-	[0.89-	CTTTTTGTAC	ID
								01	1.57]	TTCACTTGC	No:
										GCTATCACC	250
										CT[C/T]ACTG
										GGCACCCCA
										TTTGCTTTTT
										TCCCTGTCTC
										TGATGAT
chr	103390	G	C	CCDC	p.Q42	0.000	0.000	7.59	1.07	TGCCTTGGTT	SEQ
13	173			168	92E	74	69	E-	[0.33-	GTAAAATAC	ID
								01	3.46]	CAGGTCTGA	No:
										TTATTCCTTG	251
										TT[G/C]GTCT
										TCCTCTCCTT
										CTATTCTTGT
										GTCCAATAT
										ATAATGG
chr	103390	C	A	CCDC	p.E426	0.000	0.000	2.94	3.47	AGAGAAGAA	SEQ
13	257			168	4X	25	07	E-	[0.39-	TTGGAAGGC	ID
								01	31.0	AAATATAGG	NO:
									8]	AACAGAACT	252
										CTTT[C/A]CT
										GTTCATTCTT
										GTCTCCATC
										CATTTTCCCT
										TGCTCTATG
chr	103390	T	C	CCDC	p.E424	0.006	0.009	1.25	0.74	TTTCCCTTGC	SEQ
13	322			168	2G	86	27	E-	[0.5-	TCTATGCCT	ID
								01	1.08]	ACTCCATCT	NO:
										GCTTTCTGTT	253
										GC[T/C]CTTC
										AACTTCGTG
										ATCCATTTTC
										CCTTGCTCTT
										TGTCTTC
chr	103390	C	T	CCDC	p.E423	0.000	0.000	6.59	1.37	TCTATGCCT	SEQ
13	332			168	9K	49	36	E-	[0.32-	ACTCCATCT	ID
								01	5.87]	GCTTTCTGTT	NO:
										GCTCTTCAA	254
										CTT[C/T]GTG
										ATCCATTTTC
										CCTTGCTCTT
										TGTCTTCTCT
										ATCAACC
chr	103390	T	C	CCDC	p.I414	0.000	0.000	7.53	2.76	TGTTGCATG	SEQ
13	626			168	1V	98	36	E-	[0.94-	TAATCTTTTG	ID
								02	8.07]	CTTTTTGTAC	NO:
										TTTGATTGTG	255
										A[T/C]ATCAC
										CCTTACTGG
										CCACTCCAT
										CTGCTTTTTC
										CCCTGCC
chr	103390	A	T	CCDC	p.Y41	0.004	0.004	5.32	1.17	CCTGCCTCT	SEQ
13	701			168	16N	90	21	E-	[0.74-	GATGATTTTT	ID
								01	1.84]	GGTGTGATA	NO:
										GTTCTGGAA	256
										GAT[A/T]GTA
										TCTTGTTATT
										TCAGTGACA
										TACTCTGCTT
										TTTCTCTC
chr	103390	A	T	CCDC	p.L403	0.000	0.000	1.00	0.6[0	GCCCTAATT	SEQ
13	938			168	7M	25	41	E+00	.08-	TTTTCCATTT	ID
									4.42]	TTTGCCTCTG	NO:
										TTCTTTTTGC	257
										A[A/T]TATAG
										ATTCTAGGG
										CCTTTTTTAC
										ACTGTTTGA
										GATATTA
chr	103391	G	A	CCDC	p.P391	0.000	0.000	6.02	1.14	TTTTTCCAAA	SEQ
13	300			168	6L	25	22	E-	[0.15-	GCCTTTTCCA	ID
								01	8.74]	CTCTGTCTTT	No:
										GTCTTTCTGC	258
										[G/A]GCATAT
										GTTTTGCTTT
										TTCAATACT
										GCTTAAACT
										ATCATC
chr	103391	T	A	CCDC	p.K38	0.000	0.000	1.45	3.42	TTCAATACT	SEQ
13	357			168	97I	49	14	E-	[0.73-	GCTTAAACT	ID
								01	16.1	ATCATCAAT	No:
									3]	TGGCTGCTC	259
										ACAT[T/A]TT
										TCCATTGTAT
										CTGATAATT
										CCTGCTGTG
										TTGATGATG
										A
chr	103392	C	G	CCDC	p.G36	0.000	0.000	1.00	0.86	TATGTGTTGT	SEQ
13	113			168	45A	25	29	E+00	[0.11-	TTTGTACTTT	ID
									6.47]	TAACATTAC	No:
										TTGAGATCA	260
										CC[C/G]CATC
										AATTGTTTCT
										TTATTCAATT
										TGAAGTGAG
										GTAAAGA
chr	103392	C	A	CCDC	p.M34	0.021	0.026	5.76	0.81	TTGATATTA	SEQ
13	562			168	95I	08	02	E-	[0.65-	AATCAAAGA	ID
								02	1]	CCTGTACCC	No:
										CATCTGATG	261
										ATTT[C/A]AT
										TCCTTTTGGA
										AATAAGAGA
										CTTGCATATT
										TTATAGTTT
chr	103392	G	C	CCDC	p.P343	0.000	0.000	1.90	6.88	ATAGTGCTT	SEQ
13	735			168	8A	25	04	E-	[0.62-	AGCTGATCT	ID
								01	75.8	GCAGAAAAC	No:
									8]	AAGTCTAGT	262
										CCTG[G/C]TG
										TCCGGCTTG
										ATAAATTAC
										CTCCTTCTGA
										TAATGCTTC
										C
chr	103392	G	A	CCDC	p.R343	0.008	0.008	9.31	1.01	CTTAGCTGA	SEQ
13	741			168	6W	82	75	E-	[0.72-	TCTGCAGAA	ID
								01	1.42]	AACAAGTCT	No:
										AGTCCTGGT	263
										GTCC[G/A]GC
										TTGATAAAT
										TACCTCCTTC
										TGATAATGC
										TTCCTTTTCC
chr	103393	A	T	CCDC	p.D32	0.001	0.000	4.33	5.77	CTTTAATATT	SEQ
13	330			168	39E	23	21	E-	[2.03-	CAAATGTAT	ID
								03	16.3	TCCTTCTGA	NO:
									8]	ACATGGAGG	264
										TTG[A/T]TCC
										ACCGGAATA
										CCTACTTCAT
										GTGATGCTT
										TCTCTACCA
chr	103393	G	A	CCDC	p.P323	0.000	0.000	5.03	1.54	ATTCAAATG	SEQ
13	337			168	7L	25	16	E-	[0.19-	TATTCCTTCT	ID
								01	12.1	GAACATGGA	No:
									3]	GGTTGATCC	265
										ACC[G/A]GA
										ATACCTACT
										TCATGTGAT
										GCTTTCTCTA
										CCATTGGGC
										T
chr	103393	C	G	CCDC	p.V32	0.000	0.000	1.31	13.7	CCTACTTCAT	SEQ
13	383			168	22L	25	02	E-	9[0.8	GTGATGCTT	ID
								01	6-	TCTCTACCAT	No:
									220.	TGGGCTTAG	266
									58]	AA[C/G]TTTT
										GAACTCATG
										ATTTCTTCTG
										CTGAGCCTT
										CTTTCTTG
chr	103393	T	C	CCDC	p.Q31	0.000	0.000	2.20	2.49	TTTCTGTCTA	SEQ
13	580			168	56R	49	20	E-	[0.55-	TTTGATTTTA	ID
								01	11.2	ATGTAATAT	NO:
									6]	CCAACTTTG	267
										AT[T/C]GCTC
										TTTTCCCCAA
										AGATTTTCA
										TTGAAACTT
										TCAGAGAT
chr	103393	C	T	CCDC	p.V31	0.000	0.000	7.28	0.41	TCAGAATCC	SEQ
13	731			168	06M	25	59	E-	[0.06-	AGAATACTT	ID
								01	3.03]	TCGGGAACA	NO:
										TGATCTGGA	268
										TTCA[C/T]CT
										GTTCTTTCTG
										CTCTGCAGG
										CACTTTGTG
										CTGTACCTCT
chr	103394	A	G	CCDC	p.M29	0.000	0.000	2.44	4.6[0	TTCTCTAATA	SEQ
13	336			168	04T	25	05	E-	.48-	TCTTGTTCCT	ID
								01	44.1	GTTTTCTAA	NO:
									9]	GAATGCTGG	269
										AC[A/G]TATC
										AGTACAACC
										TGACAATGA
										CCTTTGCATT
										TCTTTTAG
chr	103394	T	C	CCDC	p.K28	0.003	0.004	6.99	0.85	TTCTCCAGCT	SEQ
13	421			168	76E	43	04	E-	[0.49-	TTGGCTGTG	ID
								01	1.46]	GAAGAATGC	NO:
										ATGTCCTGT	270
										CTT[T/C]TGG
										CTTGTCTTTC
										TCCATTTTTA
										CTTCTGTAA
										GCTTTTTA
chr	103394	G	A	CCDC	p.Q28	0.001	0.001	2.15	1.63	ACTCGATGT	SEQ
13	544			168	35X	72	05	E-	[0.74-	ACTGCATTTT	ID
								01	3.57]	TACTCAGCT	NO:
										GGAATGACT	271
										TCT[G/A]CTG
										CTGGATGTT
										ACCTCTCAG
										TTCTTTTTTA
										TTGCTTGCA
chr	103395	T	G	CCDC	p.K25	0.002	0.003	5.88	0.8[0	TTTGTTTTTT	SEQ
13	359			168	63T	94	69	E-	.44-	TCTATTTTTA	ID
								01	1.43]	CATTTTTTTC	NO:
										TGAATTCCC	272
										T[T/G]TGTAA
										ATCTGACTTT
										TTGAGAAAA
										AAGTTTCTC
										CCAAAAG
chr	103395	C	T	CCDC	p.R254	0.001	0.001	5.07	1.28	AGTTTCTCCC	SEQ
13	425			168	1H	72	34	E-	[0.59-	AAAAGCACA	ID
								01	2.77]	TCCTCTGATT	NO:
										TACCAAGAT	273
										GA[C/T]GATC
										CTTTCTAAG
										ATATGTGTTT
										GCCATGAAG
										TTTTCTGC
chr	103395	G	C	CCDC	p.L242	0.001	0.001	1.00	0.96	TGCCACATT	SEQ
13	789			168	0V	23	28	E+00	[0.39-	GCTTTCAGTT	ID
									2.38]	TGGTTTTTAA	NO:
										ATTGGATTC	274
										AA[G/C]TTTC
										TTCCTATGTT
										TTGTAGTAA
										ACTGCCCAC
										TGATTTTA
chr	103396	T	C	CCDC	p.K22	0.000	0.000	3.90	2.28	CTGTGAAAT	SEQ
13	163			168	95R	25	11	E-	[0.27-	TGACGACTT	ID
								01	18.9	CTTTTCCTTC	No:
									4]	ATAGTTAAA	275
										CAT[T/C]TGG
										CATTGAATA
										TAATTTCTTT
										TTCTGATAA
										CTGTGCTGT
chr	103396	C	T	CCDC	p.R214	0.003	0.005	1.77	0.68	ACTCATACT	SEQ
13	628			168	0Q	68	37	E-	[0.41-	TTTCTTGCCT	ID
								01	1.15]	ATAAACTCT	NO:
										AATGTATAG	276
										CTC[C/T]GGC
										TTTCATATTC
										AGATGACAT
										GAGGCTGGA
										GAAATCTAA
chr	103397	C	T	CCDC	p.R200	0.000	0.000	1.43	3.46	TTTGCAAGG	SEQ
13	030			168	6H	49	14	E-	[0.73-	GTCAGGATC	ID
								01	16.3]	TTTCATTTGA	NO:
										TGTGTACTG	277
										AAA [C/T]GGA
										GGTGTTGAC
										TATAGCATG
										GAACTGATT
										CTGTTAACA
										T
chr	103397	C	T	CCDC	p.D19	0.000	0.000	4.85	1.39	CCTTTACCTG	SEQ
13	280			168	23N	74	53	E-	[0.42-	AATTGTGCT	ID
								01	4.55]	GTTCCCCCA	NO:
										TACATTTCCT	278
										AT[C/T]AGTT
										GGTACACCA
										CGTTTTATTG
										CACCAGTTA
										AAACTTCA
chr	103397	T	G	CCDC	p.Q18	0.021	0.026	5.77	0.81	AGGAAGAAG	SEQ
13	387			168	87P	08	03	E-	[0.65-	TTTTGAATTT	ID
								02	1]	ACTGTACAT	NO:
										ATTGTGCCA	279
										TTT[T/G]GGG
										TCTGGAGGC
										ATTTCTTTGT
										CTCCTCTCTT
										TGTATTGG
chr	103398	G	A	CCDC	p.A16	0.000	0.000	6.79	Inf	TTTAGGTGT	SEQ
13	023			168	75V	25	00	E-	[NaN-	AGATAAAGC	ID
								02	Inf]	AGGCATGCA	NO:
										GGAACCAAA	280
										AATC[G/A]CT
										GTCTCTTTCT
										TTTCAGTAC
										CACCAGCCT
										GTTCCTTTTG
chr	103398	T	C	CCDC	p.T159	0.001	0.001	1.74	1.62	GTTTGTGTA	SEQ
13	261			168	6A	96	21	E-	[0.78-	AAATGTGTT	ID
								01	3.37]	TGTGGTTGT	NO:
										ACCTGAATA	281
										TTTG[T/C]AC
										TTCCTGGTTG
										GTTCAGTTC
										CTCATCTGA
										TTTGACAAG
										C
chr	103398	C	T	CCDC	p.D15	0.000	0.000	1.00	0.66	AGCTCATTA	SEQ
13	339			168	70N	25	37	E+00	[0.09-	TCCTTCTGAT	ID
									4.91]	ATGCATTGA	No:
										GTATTAAGC	282
										CAT[C/T]GCT
										GTTCTCCAG
										AGCCTGTAA
										AGCTTTGGG
										AGGTGGAAT
										C
chr	103398	C	A	CCDC	p.G15	0.000	0.000	3.93	9.28	GTTTCGTTG	SEQ
13	453			168	32C	49	05	E-	[1.55-	GCTTTTTGTA	ID
								02	55.5	GTTCTTCAG	No:
									3]	CTTCTAAAG	283
										GAC[C/A]CAT
										TTGGAGACT
										AGTCTCTAA
										AGTAGTTTG
										TTCAAAACC
										T
chr	103399	G	A	CCDC	p.T124	0.010	0.011	4.45	0.88	AGATAGTTC	SEQ
13	313			168	5I	05	47	E-	[0.64-	CATTATGGG	ID
								01	1.2]	AGAAACAAC	No:
										AGACTCAAT	284
										AATA[G/A]TT
										TCTGTGAAT
										GGGATTGGT
										TGATGCATT
										TCTTTCTCTG
										T
chr	103399	A	G	CCDC	p.I116	0.000	0.000	4.36	0.5[0	TTCTTCCCTT	SEQ
13	553			168	5T	49	99	E-	.12-	TCAATTTGG	ID
								01	2.04]	GATTCCTCTT	No:
										GGACTAGCT	285
										TG[A/G]TATG
										ACTGTGATT
										CTCTGCATTT
										AATCTGCTA
										TACATTCT
chr	103399	A	T	CCDC	p.N11	0.000	0.000	6.72	2.89	ATTCCTCTTG	SEQ
13	573			168	58K	98	34	E-	[0.98-	GACTAGCTT	ID
								02	8.48]	GATATGACT	No:
										GTGATTCTCT	286
										GC[A/T]TTTA
										ATCTGCTAT
										ACATTCTAG
										TATTAGGCA
										AAATAGACA
chr	103399	G	T	CCDC	p.P109	0.006	0.007	5.66	0.87	GTACCACAT	SEQ
13	761			168	6T	37	35	E-	[0.58-	ATATTAATA	ID
								01	1.29]	TAAGGCATC	No:
										AGTGAGATT	287
										GCTG[G/T]CT
										TCTTTACTTT
										CATAATTAC
										ATATTTGAC
										ACTGAGTAC
										A
chr	103399	A	G	CCDC	p.Y10	0.000	0.000	1.89	6.91	GTTTCTGAT	SEQ
13	848			168	67H	25	04	E-	[0.63-	AATTTTTTTT	ID
								01	76.1	TAATTTCCTG	NO:
									9]	CCTTTTAAA	288
										AT[A/G]TGGT
										AAAGTAAGC
										AAGTGGTTA
										TTGAAAGAC
										CCCAGGGCA
chr	103399	G	A	CCDC	p.T103	0.000	0.000	2.94	3.47	TCTTTTTACA	SEQ
13	943			168	5M	25	07	E-	[0.39-	TCTTCCTTTT	ID
								01	31.0	CTTCTGCAA	No:
									6]	TATGACTAT	289
										CC[G/A]TTGT
										CTTTTGGAG
										GTTTCCACC
										AAATGGGAC
										ACTATACTC
chr	103400	T	A	CCDC	p.D10	0.000	0.000	9.71	4.61	AACTGGCAA	SEQ
13	048			168	00V	49	11	E-	[0.93-	GTTCTCTGG	ID
								02	22.8	CATTGTAAG	No:
									4]	TGGATTCTTT	290
										GGA[T/A]CTC
										CGGCACTCT
										CTCTGTCTGT
										AGGTCTATC
										TGTGCTTTG
chr	103400	T	G	CCDC	p.K95	0.001	0.000	8.40	6.95	AAGAGTTTG	SEQ
13	198			168	0T	47	21	E-	[2.61-	TGGTTGGAC	ID
								04	18.5	TTCTTGCTCT	NO:
									3]	TTATTTGGG	291
										GCT[T/G]TAC
										TACTTCCTG
										AACTGATCT
										GTTCCATTTG
										GAATTTGAC
chr	103400	C	G	CCDC	p.D83	0.000	0.000	2.95	1.78	AGTTGAGAA	SEQ
13	532			168	9H	98	55	E-	[0.63-	ATGGTAGTG	ID
								01	5.05]	TAAGTGGCA	NO:
										CTGTGAAAT	292
										GCAT[C/G]AG
										ACGTTTCTTT
										ATCTTGATG
										CATATTTGTT
										ATGTTACTT
chr	103400	C	A	CCDC	p.D75	0.000	0.000	6.77	Inf	AAACCGACA	SEQ
13	781			168	6Y	25	00	E-	[NaN-	TTTGACAAC	ID
								02	Inf]	TCCAGAACA	NO:
										AGTTCCAAA	293
										AAAT[C/A]TT
										TTTGTTTCTG
										TGTATTTTCC
										CTTGGAAAG
										CACCTTTGC
chr	103400	T	C	CCDC	p.Q75	0.000	0.000	2.95	3.45	TGACAACTC	SEQ
13	792			168	2R	25	07	E-	[0.39-	CAGAACAAG	ID
								01	30.8	TTCCAAAAA	No:
									4]	ATCTTTTTGT	294
										TTC[T/C]GTG
										TATTTTCCCT
										TGGAAAGCA
										CCTTTGCGTT
										TTTGGTGT
chr	103400	T	A	CCDC	p.K74	0.000	0.000	2.95	3.45	TTGTTTCTGT	SEQ
13	825			168	1I	25	07	E-	[0.39-	GTATTTTCCC	ID
								01	30.9	TTGGAAAGC	No:
									11]	ACCTTTGCG	295
										TT[T/A]TTGG
										TGTACTGGT
										TGGTAACTC
										CTCTCCATTT
										GAAAGTTG
chr	103400	C	A	CCDC	p.E734	0.000	0.000	1.82	2.18	GGAAAGCAC	SEQ
13	847			168	X	74	34	E-	[0.65-	CTTTGCGTTT	ID
								01	7.38]	TTGGTGTAC	No:
										TGGTTGGTA	296
										ACT[C/A]CTC
										TCCATTTGA
										AAGTTGAAG
										ATGGGAATT
										TTCTGAACTT
chr	103401	C	G	CCDC	p.E586	0.000	0.000	2.96	3.43	ATTCCTGTCT	SEQ
13	291			168	Q	25	07	E-	[0.38-	CCTCAAGAG	ID
								01	30.7	GACCTGCAT	No:
									11]	AATTGATTTT	297
										CT[C/G]TGTA
										TCTGGTGAC
										TTATTTTGCT
										TCTGCAGAA
										AATGTCCA
chr	103401	T	C	CCDC	p.N52	0.000	0.001	5.28	0.64	ATATCTTTCC	SEQ
13	480			168	3D	98	54	E-	[0.23-	TTTCATGTA	ID
								01	1.74]	ATTCTTTCTT	No:
										CTCAGTGTT	298
										AT[T/C]CTTG
										CATCCTAAC
										TCATTCCTAT
										TTTTTAAAGT
										GTGACAT
chr	103401	A	G	CCDC	p.V37	0.001	0.001	8.33	1.01	CAGGCCCTT	SEQ
13	929			168	3A	47	45	E-	[0.44-	TACTGAATA	ID
								01	2.33]	TTTTGCCTCA	No:
										ACAATTGAT	299
										GGA[A/G]CTT
										CAACAAAAT
										GTTGGTTCCT
										ATCCAGATC
										TTGGGACTG
chr	103402	A	G	CCDC	p.Y16	0.000	0.000	5.95	1.16	TGCTCTGTAT	SEQ
13	542			168	9H	25	21	E-	[0.15-	GGCTTAGAC	ID
								01	8.89]	ACGTTTCCTC	No:
										TACTTCTGA	300
										AT[A/G]AAAC
										AATGGCAAA
										GATGAGCTG
										ATTCCATTTG
										AAGATGGC
chr	103402	A	G	CCDC	p.L167	0.000	0.000	1.00	0.82	TGTATGGCT	SEQ
13	547			168	S	25	30	E+00	[0.11-	TAGACACGT	ID
									6.13]	TTCCTCTACT	No:
										TCTGAATAA	301
										AAC[A/G]ATG
										GCAAAGATG
										AGCTGATTC
										CATTTGAAG
										ATGGCACAT
										G
chr	103402	A	G	CCDC	p.W13	0.000	0.000	3.71	0.31	GAGGGACTT	SEQ
13	638			168	7R	25	80	E-	[0.04-	ACTTGATCTT	ID
								01	2.22]	CACTTTCACT	No:
										AGTACCTGA	302
										CC[A/G]TAGT
										ATTTCACGT
										GAGAATAAA
										ATTCTATCTT
										CAAAGTTA
chr	103411	G	A	CCDC	p.A39	0.000	0.000	2.46	13.9	TATCTCAAA	SEQ
13	167			168	V	49	04	E-	1[1.9	AATAATTCC	ID
								02	6-	TAGTAAAAT	No:
									98.8	TATAAAGAA	303
									1]	AATT[G/A]CC
										ACCCAATCA
										TTTTGAATA
										ATCCAGGAC
										TCTAGAAAG
										TC
chr	103514	C	T	BIVM-	p.H76	0.007	0.005	3.78	1.48	AAGTGGATT	SEQ
13	444			ERCC	9H	84	31	E-	[1.04-	CAGAGTCTC	ID
				5				02	2.12]	TTCCTTCTTC	No:
										CAGCAAAAT	304
										GCA[C/T]GGC
										ATGTCTTTTG
										ACGTGAAGT
										CATCTCCAT
										GTGAAAAAC
chr	103701	A	G	SLC10	p.F304	0.005	0.003	3.18	1.61	ATCATGAAA	SEQ
13	648			A2	L	64	50	E-	[1.06-	TGGGATTGG	ID
								02	2.46]	CATGATTCC	No:
										TTACATCCT	305
										AAGA[A/G]T
										ATTGCGGCA
										AAGGCGAGC
										TGGAAAATG
										CTGTAGATG
										AGC
chr	110864	C	T	COL4	p.E131	0.010	0.006	3.86	1.62	CAGCGAAAC	SEQ
13	264			A1	E	29	37	E-	[1.19-	CAGGCAAGC	ID
								03	2.22]	CAGGAGGCC	No:
										CGAGCGGCC	306
										CTCT[C/T]TC
										CCCCTGGGG
										AGACAGCAG
										AGCATCATT
										CATACGCAC
										TG
chr	113201	C	T	TUBG	p.R413	0.011	0.000	1.08	14.5	GGGAAAGAC	SEQ
13	864			CP3	H	52	80	E-	[9.66-	GCGCGTGGG	ID
								30	21.7	AAAGACGTG	No:
									5]	CATGGGAAA	307
										GTCG[C/T]GC
										GTGGGAAAG
										TCGCGCGTG
										GGAAAGTCG
										CGCGTGGGA
										AA
chr	114175	G	A	TMCO	p.P436	0.012	0.008	3.24	1.39	CGCAGGACG	SEQ
13	013			3	P	01	69	E-	[1.04-	TGCAGCTCG	ID
								02	1.85]	GGCTCTTCA	No:
										TGGCCGTCA	308
										TGCC[G/A]AC
										TCTCATACA
										GGCGGGCGC
										CAGTGCATC
										TTCTAGGTA
										AA
chr	212161	G	A	EDDM	p.V13	0.007	0.004	1.38	1.62	CTTCAGCTA	SEQ
14	36			3A	3I	35	56	E-	[1.12-	CATTGAATT	ID
								02	2.34]	CCATTGTGG	No:
										CGTAGATGG	309
										ATAT[G/A]TT
										GATAACATA
										GAAGACCTG
										AGGATTATA
										GAACCTATC
										AG
chr	233538	G	A	REM2	p.T39	0.009	0.004	1.55	2.02	TTTCTTTGCC	SEQ
14	96				T	07	52	E-	[1.44-	CTCCCATTTT	ID
								04	2.82]	ATTTTAGAA	No:
										GCAGATGCC	310
										AC[G/A]CTAC
										TAAAGAAGT
										CAGAGAAAC
										TGTTGGCAG
										AGTTGGACC
chr	244643	C	T	DHRS	p.T29	0.008	0.001	3.09	7.44	CTGCTGTCA	SEQ
14	24			4L2	T	33	13	E-	[5.09-	ACCCTTTCTT	ID
								17	10.8	TGGAAGCCT	No:
									9]	AATGGATGT	311
										CAC[C/T]GAG
										GAGGTGTGG
										GACAAGGTG
										AGAGGGGAT
										TAAAGAAGC
										G
chr	247723	C	T	NOP9	p.R413	0.007	0.004	3.19	1.61	GGGCCACCC	SEQ
14	73				C	482	658	E-	[1.01-	AGGGGTAGT	ID
								02	2.45]	CATTGCCCT	No:
										GGTGGGGGC	312
										CTGT[C/T]GC
										AGAGTTGGG
										GCCTACCAA
										GCCAAGGTC
										CTACAGCTC
										TT
chr	449751	G	A	FSCB	p.P363	0.010	0.000	7.71	Inf	AGGAGACTT	SEQ
14	03				L	29	00	E-		TTCAGCTGG	ID
								62		TGGAGGCAG	No:
										AATTTCAGC	313
										AGGA[G/A]G
										CTCTTCTGA
										AGGGGACTC
										TTCAGCTGA
										TGGAGGCAG
										AAT
chr	449751	G	A	FSCB	p.P359	0.024	0.000	1.52	2806	AGCTGGTGG	SEQ
14	15				L	51	01	E-	.41[3	AGGCAGAAT	ID
								144	91.3	TTCAGCAGG	No:
									8-	AGGCTCTTC	314
									2012	TGAA[G/A]G
									3.7]	GGACTCTTC
										AGCTGATGG
										AGGCAGAAT
										TTCAGCCAG
										AAG
chr	505810	A	C	VCPK	p.Y18	0.010	0.006	2.01	1.48	ACTACAAAG	SEQ
14	11			MT	8D	05	79	E-	[1.08-	ATAATAGAG	ID
								02	2.04]	TACTTAATA	No:
										CTTACCTCA	315
										AAAT[A/C]TT
										TTTTCTCAAT
										TTCTGGATTT
										TTCCCCATTG
										TTCGTTGT
chr	524954	C	T	NID2	p.R830	0.005	0.003	4.83	1.61	GATGCAAGT	SEQ
14	81				Q	15	20	E-	[1.04-	ATGCCGGTC	ID
								02	2.51]	ATCTGCAAA	No:
										CTCATAACC	316
										ACTC[C/T]GG
										CACTCACAC
										CTGTAGCTT
										CCAGGCAAG
										TTGATACAT
										AC
chr	524963	T	C	NID2	p.D75	0.011	0.007	2.33	1.44	CATGTGGCT	SEQ
14	99				6G	03	71	E-	[1.06-	CCCATCATA	ID
								02	1.94]	GCAAGGATT	No:
										CCCCGGAGT	317
										GGGG[T/C]CT
										GAATCCTCT
										GCATGAGTA
										GAGGGGAAA
										TAAAAGCAC
										AA
chr	525096	C	T	NID2	p.R493	0.011	0.008	4.93	1.35	AGTGGCATA	SEQ
14	01				K	76	72	E-	[1.01-	GTCCGTGCA	ID
								02	1.81]	GAAGGCATG	No:
										CCGGGAGCA	318
										TTGT[C/T]TG
										TGGTTGTGTT
										CACAGGTTT
										CCTTGTTGG
										CAGCATTAT
										A
chr	609218	T	G	C14orf	p.E462	0.006	0.004	4.35	1.52	TAAGAAAAG	SEQ
14	36			39	D	86	52	E-	[1.04-	AAAGTCCAG	ID
								02	2.23]	GGGATTCCT	No:
										TTTCTGTTTG	319
										AAC[T/G]TCA
										GGTACTGCA
										TTTCTATTTC
										TGTTACTGA
										GAAATAAGA
chr	622448	C	T	SNAP	p.T253	0.005	0.003	4.52	1.72	AATGATGGA	SEQ
14	54			C1	M	21	03	E-	[0.97-	GAAGAAAAA	ID
								02	2.84]	ATGGAAGGA	No:
										AATTCACAA	320
										GAAA[C/T]GG
										AGGTCAGAA
										AACTTTGCA
										ATTCATATT
										ATGTGTGGC
										TG
chr	695216	C	T	DCAF	p.R589	0.006	0.003	7.18	1.78	TGGGGCACT	SEQ
14	37			5	H	86	88	E-	[1.21-	GGGCTTGTC	ID
								03	2.6]	TTCTCGGGTT	No:
										GTCTTCTGTC	321
										GG[C/T]GCCG
										CATGGCATT
										CCGCTGCCA
										GGTAGAGGC
										TCGGCGTTC
chr	704189	C	T	SMOC	p.P77L	0.005	0.003	3.93	1.61	GAGTCCATG	SEQ
14	85			1		39	36	E-	[1.04-	TGTGAGTAC	ID
								02	2.47]	CAGCGAGCC	No:
										AAGTGCCGA	322
										GACC[C/T]GA
										CCCTGGGCG
										TGGTGCATC
										GAGGTAGAT
										GCAAAGGTG
										AG
chr	751512	C	T	AREL1	p.V50	0.007	0.004	1.58	1.74	GAGACTTTG	SEQ
14	52				M	157	135	E-	[1.08-	CAAGACCGG	ID
								02	2.67]	GGATCCAGG	No:
										TAATTTCCCC	323
										GCA[C/T]GTA
										GTCATAAAT
										AGTCCGGTC
										CCCTCGGCG
										CTCGCGGTC
										C
chr	860881	C	A	FLRT2	p.L107	0.006	0.003	2.85	1.61	CTACCTGTA	SEQ
14	77				I	13	82	E-	[1.07-	TGGCAACCA	ID
								02	2.41]	ACTGGACGA	No:
										ATTCCCCAT	324
										GAAC[C/A]TT
										CCCAAGAAT
										GTCAGAGTT
										CTCCATTTGC
										AGGAAAACA
										A
chr	888929	C	T	SPATA	p.R211	0.005	0.003	4.13	1.59	CTGAACTCT	SEQ
14	32			7	R	39	41	E-	[1.03-	TTTCTAACA	ID
								02	2.44]	AACAATTGC	No:
										CATTCACTC	325
										CTCG[C/T]AC
										TTTAAAAAC
										AGAAGCAAA
										ATCTTTCCTG
										TCACAGTAT
										C
chr	891108	T	C	EML5	p.V13	0.009	0.006	3.12	1.45	AGTGAGTTT	SEQ
14	01				61V	56	63	E-	[1.05-	TCCTTACCTC	ID
								02	2]	TATAGGTCT	No:
										CTTTTTCTTG	326
										CC[T/C]ACAT
										TGTTTGTCTG
										GAGTTTCTCT
										GGCTGTGGT
										GGGGCCC
chr	101004	A	G	BEGAI	p.F568	0.005	0.000	2.13	607.	CTGTCCTTGC	SEQ
14	386			N	L	88	01	E-	53[8	GGCTCAGCC	ID
								33	2.17-	CCGAGCCAC	No:
									4491	CAGTCCGCG	327
									.9]	GAA[A/G]GG
										CCTGCTGGG
										GGCTGAGGC
										GGGCGGCAG
										GATGCATTT
										CC
chr	103593	T	A	TNFAI	p.V79	0.009	0.000	1.74	Inf	GTGGGCTGG	SEQ
14	342			P2	E	80	00	E-		GGCCGGGGC	ID
								07		TGACGCGGC	No:
										TTTCCCGGC	328
										GCAG[T/A]GG
										AGGAGCTGA
										AGGCGGCGC
										TGGAGCGCG
										GGCAGCTGG
										AG
chr	105415	C	T	AHNA	p.K21	0.011	0.000	4.90	43.0	GGTCCCCCT	SEQ
14	242			K2	82K	27	26	E-	7[27.	GCATGGAGG	ID
								47	03-	GGAGACTCA	No:
									68.6	TGTCGGCCT	329
									2]	CCAC[C/T]TT
										GGGTGGAGA
										CACATCCAC
										CGAGGCCTC
										GATGGACTT
										GC
chr	105415	T	C	AHNA	p.K21	0.019	0.000	7.30	21.3	CACCCCAAA	SEQ
14	333			K2	52R	61	94	E-	6[15.	CGACGGCAT	ID
								63	62-	CTTGAACTT	No:
									29.1	GGGCATTTT	330
									9]	GAAC[T/C]TG
										CTGTCTTTGG
										TAGTCAGGT
										CCTTGTTGG
										CCAGGGTCA
										G
chr	105415	A	T	AHNA	p.D20	0.005	0.003	1.74	1.74	AGGGGAGAC	SEQ
14	752			K2	12E	64	25	E-	[1.14-	TCACGTCGG	ID
								02	2.65]	CCTCCACCTT	No:
										GGGTGCAGG	331
										CAC[A/T]TCC
										ACCGAGGCC
										TCGATGGAC
										CTCCCTGGG
										GCCGATACC
										C
chr	105418	G	C	AHNA	p.L120	0.008	0.001	3.11	4.88	GGTCAGCGG	SEQ
14	170			K2	6L	82	82	E-	[3.41-	AAGGGGGCT	ID
								13	6.97]	GAATGCTGA	No:
										GGTCAGTGG	332
										TCTT[G/C]AG
										GTCCCCCTG
										CATGGAGGG
										GAGACTCAC
										GTCGGCCTC
										CA
chr	315155	G	A	LOC28	p.L124	0.011	0.000	2.03	Inf	TGGGATCAG	SEQ
15	19			3710	F	52	00	E-		TGCGGCCTG	ID
								51		TCGTCTGCT	No:
										GTTGTCATG	333
										TGGA[G/A]CT
										CAGCAAACG
										GTGGGAGTC
										CTAGGGGAC
										AACATACAC
										AG
chr	387768	T	A	FAM9	p.G42	0.007	0.000	7.32	61.2	ATCCATATG	SEQ
15	33			8B	5G	35	12	E-	9[23.	GAGGAGGTG	ID
								27	77-	GTGGTGGTG	No:
									158.	GTGGTGGTG	334
									06]	GTGG[T/A]GG
										AGGAGGTGG
										ATATAGAAG
										ATACTAAAA
										ACTATAAAA
										AT
chr	418623	G	A	TYRO3	p.T458	0.008	0.005	1.15	1.6[1	CCCTGGCCC	SEQ
15	46				T	33	24	E-	.13-	TCATCCTGCT	ID
								02	2.26]	TCGAAAGAG	No:
										ACGGAAAGA	335
										GAC[G/A]CG
										GTTTGGGTA
										AGGGGATGG
										GGATGTGGA
										GGGAGAGGC
										AG
chr	436533	C	T	ZSCAN	p.R842	0.005	0.003	4.15	1.58	AGGGGCTTA	SEQ
15	05			29	Q	39	41	E-	[1.03-	CTTGGGAGC	ID
								02	2.44]	TGACTGTGT	No:
										CAGAAGCTT	336
										TTCC[C/T]GT
										GCATGGATT
										TCTCCGTGCT
										TATTAAGGG
										CAGAGCTTT
										T
chr	484704	G	T	MYEF	p.A2E	0.026	0.000	2.09	Inf	GCCACCAGT	SEQ
15	30			2		23	00	E-		GGCCCCGGG	ID
								39		CACCTCGGC	No:
										CTTGTTGGC	337
										GTCC[G/T]CC
										ATCCCGCCG
										CCGCTGCCT
										CCGCCTCGG
										CCGCCTGAG
										CT
chr	525107	A	G	MYO5	p.L129	0.005	0.003	3.12	1.67	TTACACTTG	SEQ
15	96			C	2L	15	08	E-	[1.08-	ACTTCACTTT	ID
								02	2.6]	CAGTTTCAA	No:
										ATTGTTTCTT	338
										CA[A/G]GTGG
										TCACTGGCC
										TCCTGCATTT
										CTTGAATCTT
										ATCAATC
chr	651578	G	A	PLEK	p.S420	0.010	0.007	1.60	1.47	AACGGCTAT	SEQ
15	74			HO2	S	78	36	E-	[1.08-	ATCGGGCCC	ID
								02	1.99]	AGCTGGAGG	No:
										TGAAGGTGG	339
										CCTC[G/A]GA
										ACAGACGGA
										GAAACTGTT
										GAACAAGGT
										GCTGGGCAG
										TG
chr	720235	G	A	THSD4	p.V52	0.005	0.003	2.01	1.83	GATACACCA	SEQ
15	02				6M	53	02	E-	[1.05-	GCAGCCAAA	ID
								02	2.99]	CCCAGGCGT	No:
										GCACTACGA	340
										GTAC[G/A]TG
										ATCATGGGG
										ACCAACGCC
										ATCAGCCCC
										CAGGTGCCA
										CC
chr	721922	C	G	MYO9	p.R109	0.005	0.002	2.23	1.89	GTAATCTCT	SEQ
15	05			A	8P	21	75	E-	[1.07-	CCATTTCTGC	ID
								02	3.13]	TGGATAACG	No:
										ATGGCTGCA	341
										GCC[C/G]GTA
										ACTCCAAGT
										ACCGCTGCC
										TCTCTAAGT
										GAGCACGCC
										A
chr	725021	T	C	PKM	p.N15	0.005	0.003	3.24	1.61	CACCACCTT	SEQ
15	15				5S	64	52	E-	[1.05-	GCAGATGTT	ID
								02	2.45]	CTTGTAGTC	No:
										CAGCCACAG	342
										GATG[T/C]TC
										TCGTCACAC
										TTTTCCATGT
										AGGCGTTAT
										CCAGCGTGA
										T
chr	725136	T	A	PKM	p.T36S	0.017	0.011	2.57	1.5[1	CTTGGCCTC	SEQ
15	12					16	53	E-	.16-	ACTAGCAAA	ID
								03	1.93]	GACCGCTCA	No:
										GAGCTGAAT	343
										ACGG[T/A]GT
										GCCCTGGAG
										AGCTGCACA
										AGGATTAAG
										GAAAAAGCT
										GA
chr	759815	C	A	CSPG4	p.G63	0.005	0.000	7.77	Inf	TCCATCGCT	SEQ
15	11				2V	15	00	E-		GACCCGGAA	ID
								31		CGTCAAGTC	No:
										CTGTGCAGG	344
										ACCA[C/A]CG
										CGGTGGACA
										TAGACTAGG
										CTGCCGGCC
										TCCAACTCC
										CG
chr	759820	A	G	CSPG4	p.H45	0.006	0.004	4.39	1.52	TGCGCAGCT	SEQ
15	53				1H	86	53	E-	[1.04-	CAGCCTCCA	ID
								02	2.23]	TCAGGTCCA	No:
										GCGTGGGCT	345
										GCAC[A/G]TG
										CCTCCACTC
										AAGCCAGGC
										TGTGCCCCC
										CTCGGCCAC
										CA
chr	784613	C	T	IDH3A	p.R360	0.006	0.003	7.88	1.74	AGGCAATGC	SEQ
15	24				C	86	96	E-	[1.18-	AAAATGCTC	ID
								03	2.55]	AGACTTCAC	No:
										AGAGGAAAT	346
										CTGT[C/T]GC
										CGAGTAAAA
										GATTTAGAT
										TAACACTTC
										TACAACTGG
										CA
chr	790589	A	T	ADAM	p.A11	0.007	0.000	2.49	10.5	GAGGCTCTG	SEQ
15	44			TS7	03A	89	80	E-	6[6.0	TGGCAGGCA	ID
								11	4-	CGGGGCTAC	No:
									18.4	CCGTGGAGG	347
									9]	GCGC[A/T]GC
										AGGATGGCT
										GTGTGGTGG
										GGGTGTCCG
										GTCCCCTGT
										CC
chr	796037	G	A	TMED	TMED	0.006	0.004	3.23	1.54	GGAGGTGGA	SEQ
15	60			3	3(NM_	86	47	E-	[1.05-	GCAGGGCGT	ID
					007364:			02	2.26]	GAAGTTCTC	No:
					exon1:					CCTGGATTA	348
					c.1					CCAG[G/A]TG
					68 + 1					AGGCCGGGC
					G > A)					GCCCGGCAG
										CGCTCCCTTC
										TCCCTCCACT
chr	891697	G	A	AEN	p.G10	0.006	0.004	2.72	1.58	TGGATCTGG	SEQ
15	38				0R	62	20	E-	[1.07-	CAGTGCCCC	ID
								02	2.33]	ATGCAGCAG	No:
										AAGGCCTGC	349
										TCCC[G/A]GG
										AAAGCCTCA
										GGGCCCTTG
										CCCAGCAAG
										TGTGTGGCT
										AT
chr	102346	C	T	OR4F6	p.R54	0.005	0.003	2.56	1.62	GGGAAATCT	SEQ
15	082				C	88	63	E-	[1.07-	CCTCATTGT	ID
								02	2.45]	GCTAACTGT	No:
										GACCTCTGA	350
										CCCT[C/T]GT
										TTACAGTCC
										CCCATGTAC
										TTCCTGCTG
										GCCAACCTT
										TC
chr	315001	C	T	ITFG3	p.R547	0.005	0.003	3.86	1.62	AGACAGTGA	SEQ
16					W	39	35	E-	[1.05-	CCAAGCCAT	ID
								02	2.49]	CAGGGACCG	No:
										GTTCTCCCG	351
										GCTG[C/T]GG
										TACCAGAGT
										GAGGCGTAG
										AGGCACGCC
										AGCCAGAGC
										CT
chr	863362	C	G	PRR25	p.P237	0.020	0.000	1.86	Inf	GACATCCCC	SEQ
16					R	34	00	E-		TCTGCTATTG	ID
								108		CTGCGGGAC	No:
										CGGCAAGGA	352
										CGC[C/G]GGA
										CCGACACGG
										CCTCCCCAT
										CCCTGGGTC
										CACCCCGAC
										T
chr	225857	G	A	MLST8	p.G27	0.005	0.002	7.86	1.86	GAGCGGCAA	SEQ
16	5				5S	39	90	E-	[1.21-	CCCCGGGGA	ID
								03	2.88]	GTCCTCCCG	No:
										CGGCTGGAT	353
										GTGG[G/A]GC
										TGCGCCTTCT
										CGGGGGACT
										CCCAGTACA
										TCGTCACTG
										G
chr	228764	A	C	DNAS	p.D19	0.005	0.003	3.19	1.6	TACGACGTG	SEQ
16	9			EIL2	7A	64	51	E-	[1.06-	TACCTGGAC	ID
								02	2.46]	GTGATCGAC	NO:
										AAGTGGGGC	354
										ACCG[A/C]CG
										TAAGCCCAC
										CCCTCGGTC
										CCGGGGTCC
										CTGCAGGCG
										CG
chr	236959	C	T	ABCA3	p.R288	0.014	0.009	1.71	1.56	GAGTGTTGG	SEQ
16	2				K	46	32	E-	[1.2-	GGAGCCAAA	ID
								03	2.03]	GCGGGCAGT	NO:
										CACCTTCAG	355
										CCTC[C/T]TT
										TCCTTCTCCT
										GCACGACAG
										CACGGGCAA
										TGGTGAGCG
										C
chr	284851	G	T	PRSS4	p.A10	0.016	0.000	6.97	Inf	GAGAGGAGG	SEQ
16	5			1	A	67	00	E-		CCATGGGCG	ID
								73		CGCGCGGGG	NO:
										CGCTGCTGC	356
										TGGC[G/T]CT
										GCTGCTGGC
										TCGGGCTGG
										ACTCGGGAA
										GCCGGGTGA
										GC
chr	363905	C	T	SLX4	p.P152	0.005	0.002	4.17	2.04	CTTCGGGCT	SEQ
16	8				7P	15	53	E-	[1.31-	TCTGAGCTC	ID
								03	3.18]	CACCAGCGC	NO:
										TTGGCATCT	357
										GGGC[C/T]GG
										AGGAGGGGT
										CTCTGGAGG
										CCTCTGCTCT
										TCCCCGTCC
										C
chr	363937	T	A	SLX4	p.I142	0.011	0.001	8.31	11.0	GAGAGGGGC	SEQ
16	8				1F	76	07	E-	9[7.9-	TCCATGTGC	ID
								30	15.5	CAGCAGCAG	NO:
									6[	TCGTCAATT	358
										GGAA[T/A]TG
										GGGGGTCAC
										TGTCCAGTG
										GGGGGCTTC
										TGTTGGCCT
										GA
chr	364081	C	G	SLX4	p.E942	0.005	0.002	1.53	2.14	TGGCCAAGC	SEQ
16	5				Q	39	53	E-	[1.39-	GCCTCCTCT	ID
								03	3.31]	GGCGCCTCC	NO:
										TGCTCAGGG	359
										GCCT[C/G]TG
										CTCCCCGTG
										CCCCTGAGT
										GCTGGCCCT
										GGGGTGGCG
										GG
chr	370719	G	A	DNAS	p.V18	0.008	0.004	4.80	1.69	CGCATGTCC	SEQ
16	1			E1	5I	33	95	E-	[1.19-	CAGGGCCAC	ID
								03	2.39]	AGGCAGCGT	No:
										TTCCTGGTA	360
										GGAC[G/A]TC
										ATGTTGATG
										GGCGACTTC
										AATGCGGGC
										TGCAGCTAT
										GT
chr	373608	C	T	TRAP1	p.R128	0.005	0.002	9.00	1.91	CATTTCTGG	SEQ
16	5				H	15	70	E-	[1.22-	CAGTGCTTG	ID
								03	2.97]	GCCGTCAGA	No:
										CACCAGTTT	361
										GTGA[C/T]GC
										AGTTTTTCCA
										AGGCATCGC
										TGGCATTGG
										AGATCAGCT
										C
chr	491077	A	G	UBN1	p.R262	0.024	0.000	1.26	2748	GCTAAAGAA	SEQ
16	7				G	02	01	E-	.75[3	ATTTCAGAA	ID
								141	83.2	AGAGAAAGA	No:
									6-	GGCTCAGAA	362
									1971	AAAA[A/G]G
									4.18]	GGAGGAGGA
										GCATAAGCC
										TGTTGCGGT
										CCCATCAGC
										GGA
chr	209965	G	A	DNAH	p.D25	0.006	0.004	4.15	1.51	CGATGTCAG	SEQ
16	25			3	13D	62	39	E-	[1.03-	CCTTCTCGTC	ID
								02	2.23]	AGCAGGGAA	No:
										GATGTTAGG	363
										CAC[G/A]TCA
										CCTGTGTTC
										AGAAGCATG
										TTGATGTCCT
										CCACGAATG
chr	209965	G	A	DNAH	p.A24	0.007	0.004	1.02	1.68	TGATGTCCT	SEQ
16	88			3	92A	11	23	E-	[1.16-	CCACGAATG	ID
								02	2.45]	ATTCATCCTT	No:
										GATCTGGTT	364
										GTC[G/A]GCG
										AAGAGGAAC
										ACGGTGCTC
										TTGGTGGCC
										ACACCGACC
										T
chr	217476	A	C	OTOA	p.T706	0.007	0.000	5.19	75.1	CCTTCTGCA	SEQ
16	33				P	35	10	E-	3[37.	AGCAGCTTC	ID
								35	62-	CAAGATGGC	No:
									150.	CAGGACCCT	365
									01]	GCCC[A/C]CT
										AAAGAATTC
										CTCTGGGCT
										GTCTTTCAGT
										CTGTTCGGA
										A
chr	217476	G	T	OTOA	p.E708	0.007	0.000	1.12	413.	GCAAGCAGC	SEQ
16	39				X	35	02	E-	18[9	TTCCAAGAT	ID
								41	8.71-	GGCCAGGAC	NO:
									1729	CCTGCCCAC	366
									.48]	TAAA[G/T]AA
										TTCCTCTGG
										GCTGTCTTTC
										AGTCTGTTC
										GGAACAGCA
										G
chr	217476	G	A	OTOA	p.Q71	0.007	0.000	5.17	136.	GGACCCTGC	SEQ
16	62				5Q	35	05	E-	27[5	CCACTAAAG	ID
								38	6.69-	AATTCCTCT	NO:
									327.	GGGCTGTCT	367
									58]	TTCA[G/A]TC
										TGTTCGGAA
										CAGCAGTGA
										TAAGATCCC
										CAGCTATGA
										CC
chr	289438	C	G	CD19	p.P102	0.019	0.000	1.99	Inf	CAACAGATG	SEQ
16	83				R	36	00	E-		GGGGGCTTC	ID
								114		TACCTGTGC	No:
										CAGCCGGGG	368
										CCCC[C/G]CT
										CTGAGAAGG
										CCTGGCAGC
										CTGGCTGGA
										CAGTCAATG
										TG
chr	289962	G	C	LAT	p.L15F	0.017	0.000	7.89	Inf	AGGCCACGG	SEQ
16	27					89	00	E-		CTGCCAGCT	ID
								80		GGCAGGTGG	NO:
										CTGTCCCCG	369
										TCTT[G/C]GG
										GGGGGCCAG
										CAGACCCTT
										GGTGAGTGC
										CTGGGGTGG
										CT
chr	307932	C	G	ZNF62	p.Q79	0.014	0.000	4.59	1291	CTGCCTCTG	SEQ
16	73			9	2H	22	01	E-	.24[1	GAGGGGGGT	ID
								78	78.8	CCTCGGGAT	NO:
									1-	TGGGGGGTT	370
									9324	TTTC[C/G]TG
									.5]	GGTGTGGGT
										TTCTTGGTGC
										CGGGTGAGG
										GCCACGCGG
										T
chr	307942	G	T	ZNF62	p.T481	0.022	0.000	7.33	Inf	AGCTCTTGC	SEQ
16	06			9	T	55	00	E-		CGCACTCGG	ID
								134		GGCACTTGT	NO:
										AGGGCTTCT	371
										CGCC[G/T]GT
										GTGCGTGCG
										GCGGTGCTG
										GATAAGGTG
										GGAGCTGCG
										GA
chr	620552	G	A	CDH8	p.P24S	0.015	0.000	1.88	451.	ACTTGAGAC	SEQ
16	38					93	0 4	E-	14[1	TGATTCATC	ID
								89	64.2	GGAGCCATG	No:
									8-	TAAATGCAA	372
									1238	GGGG[G/A]A
									.87]	AGAGTAATC
										CATAATATT
										ATTAATGGA
										GTCCAGAGA
										TCC
chr	672368	C	T	ELMO	p.T600	0.006	0.004	4.80	1.48	CTGATCCGC	SEQ
16	72			3	M	86	65	E-	[1.01-	CAGCAGCGC	ID
								02	2.16]	TTGCTCCGC	No:
										CTCTGTGAG	373
										GGGA[C/T]GC
										TCTTCCGCA
										AGATCAGCA
										GCCGGCGGC
										GCCAGGGTC
										TC
chr	689615	C	T	TANG	p.R745	0.008	0.006	3.26	1.45	ATACCCTGA	SEQ
16	76			O6	C	82	09	E-	[1.04-	TCCGGTCAT	ID
								02	2.03]	CCAAGAACT	No:
										CGCTGTTGA	374
										TCTC[C/T]GC
										ATCACCATC
										TCTACCCAT
										GGAGCCTTT
										GCCACTGAG
										GC
chr	705088	A	G	FUK	p.T772	0.009	0.006	1.39	1.54	TGAGCTGTG	SEQ
16	51				A	31	05	E-	[1.11-	GCTGGCGGT	ID
								02	2.15]	GGGGCCTCG	No:
										GCAGGATGA	375
										GATG[A/G]CT
										GTGAAGATA
										GTGTGCCGG
										TGCCTGGCT
										GACCTGCGG
										GA
chr	708947	C	T	HYDIN	p.P393	0.025	0.000	4.43	656.	GGCAGATGG	SEQ
16	71				7P	98	04	E-	67[9	GCAAGGTGC	ID
								89	1.63-	TCCGCCCTTT	No:
									4706	TGCTACCAG	376
									.3]	GAC[C/T]GGA
										CCTTGCTCTC
										CAGGTGGCA
										GGTTGGGAA
										TCCTGAGAG
chr	708970	C	T	HYDIN	p.R383	0.005	0.000	1.11	Inf	TGAGGTATC	SEQ
16	62				2H	39	00	E-		TTCTGAGAC	ID
								32		CCAGCTGAA	No:
										TTCCAGCTG	377
										GACA[C/T]GT
										CCTGAATTA
										ATCACATCG
										AACCTGCAA
										ATCGATCAG
										GG
chr	709350	C	T	HYDIN	p.R295	0.005	0.002	9.20	2.95	AGGCCACAG	SEQ
16	93				4R	88	00	E-	[1.93-	GCAGGAGCG	ID
								06	4.51]	TGACATTGC	No:
										GGAGAAGAA	378
										CTAC[C/T]CT
										GGATTCCTG
										TCTGCAGAG
										ACAAAAGGA
										AAGTTGCAA
										TT
chr	709550	G	A	HYDIN	p.I240	0.017	0.000	2.60	Inf	TCTCAGACA	SEQ
16	79				0I	40	00	E-		TTGTTTGTTC	ID
								94		CCTAACAGA	No:
										TATTTTCCTT	379
										TC[G/A]ATTG
										TCTCCATCTT
										GACATCCAC
										TTTGGTGAG
										CGGAGGAA
chr	709960	G	A	HYDIN	p.S193	0.006	0.001	1.77	5.05	CGATGTCCT	SEQ
16	23				6L	37	27	E-	[3.17-	CTTTGTGCTA	ID
								09	8.05]	TTGGAGGTT	No:
										CCCTGATCT	380
										GAT[G/A]AG
										GTTATATCTT
										CCTCTTCTGC
										CAGGTAGCA
										AAGGATGAA
chr	711012	G	A	HYDIN	p.A71	0.005	0.000	2.94	93.9	AGAGCAAGC	SEQ
16	11				3V	88	06	E-	2[40.	TGGGGAGCA	ID
								29	44-	ATACCTTGC	No:
									218.	TGTAATTAA	381
									11]	GAGC[G/A]CC
										AGCACCTCT
										TCTCCGATG
										CCCTCCACG
										TCCACCACG
										AG
chr	851007	C	T	KIAA0	p.D40	0.005	0.001	1.06	3.2[2	CACCCCCTG	SEQ
16	97			513	D	15	61	E-	.03-	TGCTGCAGG	ID
								05	5.03]	ACGGCGATG	No:
										GCTCCCTGG	382
										GGGA[C/T]GG
										TGCATCAGA
										GAGTGAGAC
										CACTGAGTC
										TGCGGACAG
										TG
chr	887197	T	C	MVD	p.K36	0.011	0.007	1.19	1.51	CTGGGTGAG	SEQ
16	26				8K	03	34	E-	[1.11-	CCCCAGGCC	ID
								02	2.04]	TCACCTGAG	No:
										TGACAATGA	383
										TGTA[T/C]TT
										GACCCCACC
										GGGGGTCGG
										CTCCATGGC
										CAGCGCAGC
										CT
chr	168770	C	T	SMYD	p.V64	0.006	0.003	2.00	1.95	TGTAGGTCC	SEQ
17	7			4	51	86	53	E-	[1.33-	TGTAACCGA	ID
03	2.87								2.87]	GAGACCAGG	NO:
										TGGTCCCTG	384
										CTGA[C/T]GG
										CGGATTCTG
										CACAAGATC
										TGCTGCCAC
										AGCGCAGCA
										CG
chr	227571	G	C	SGSA1	p.R530	0.005	0.000	8.71	571.	TGTCGGCGC	SEQ
17	9			2	R	88	01	E-	47[7	TGGTGCACC	ID
								33	7.29-	ATAGCGTTA	NO:
									4225	TCCCACCTG	385
									.3]	ACCG[G/C]CC
										CCCGGGGGC
										CTCCGCGGG
										CCTCACCAA
										GGACGTGTG
										GA
chr	319577	A	T	OR3A1	p.F34I	0.011	0.006	5.13	1.74	CTGAGGTTG	SEQ
17	7					76	79	E-	[1.3-	CCCCTGACC	ID
								04	2.33]	GTGACCAGG	NO:
										TAGGCAAAG	386
										AGGA[A/T]G
										AGCACAAAG
										ACAACTGGC
										TGCAGCCCT
										GGCGCCTCC
										AGC
chr	722237	G	A	NEUR	p.L122	0.006	0.003	1.18	1.72	CCTGGTCCT	SEQ
17	4			L4	5F	13	57	E-	[1.15-	GTTCCTTCTC	ID
								02	2.58]	TCTGGCTCCT	NO:
										ACTCACCTT	387
										GA[G/A]ACC
										GTTGTGGAA
										GACCCCACG
										GCCCCGCAG
										CAGCCAGGC
										T
chr	819320	G	A	RANG	p.Q17	0.005	0.003	9.03	1.78	ATCTGTCAC	SEQ
17	3			RF	0Q	88	31	E-	[1.18-	CTGCACCCT	ID
								03	2.69]	GGAGCCTGG	NO:
										GTGACTTTG	388
										AACA[G/A]CT
										GGTGACCAG
										TCTGACCCTT
										CACGATCCT
										AACATCTTT
										G
chr	117846	C	T	DNAH	p.A35	0.008	0.005	4.28	1.45	TCACCGTGA	SEQ
17	88			9	88A	09	58	E-	[1.02-	CCAGGGATG	ID
								02	2.07]	GCCTGGAGG	NO:
										ACCAGTTGC	389
										TGGC[C/T]GC
										TGTGGTCAG
										CATGGAGAG
										GCCAGACTT
										GGAGCAGCT
										GA
chr	142048	C	T	HS3ST	p.C11	0.005	0.002	3.72	2[1.2	GGCAGCGCA	SEQ
17	68			3B1	C	39	71	E-	9-	TGGGGCAGC	ID
								03	3.1]	GCCTGAGTG	NO:
										GCGGCAGAT	390
										CTTG[C/T]CT
										CGATGTCCC
										CGGCCGGCT
										CCTACCGCA
										GCCGCCGCC
										GC
chr	171844	C	T	COPS3	p.A2A	0.008	0.005	4.22	1.46	AGAGCTGTC	SEQ
17	95					09	56	E-	[1.03-	GGACACTGT	ID
								02	2.07]	TCACGAACT	NO:
										GCTCCAGGG	391
										CAGA[C/T]GC
										CATGTTTTCC
										CCCGGGCGG
										CCCGAGCGG
										CGAAGGCAG
										C
chr	188746	C	T	FANTS	p.D81	0.011	0.000	1.70	1177	TGGCTCCAG	SEQ
17	89			3G	9N	03	01	E-	.01[1	GCTGGGACA	ID
								63	62.2	TGCTGCTAG	No:
									1-	GGGTCTTTG	392
									8540	CGGT[C/T]CC
									.78]	GGGGGGCTT
										GAGCCCTCC
										GTTTAGAAT
										CCGATGAGG
										CC
chr	212039	G	A	MAP2	p.M90	0.009	0.004	9.33	2.28	TGGTAGAGA	SEQ
17	61			K3	I	56	22	E-	[1.64-	AGGTGCGGC	ID
								06	3.16]	ACGCCCAGA	NO:
										GCGGCACCA	393
										TCAT[G/A]GC
										CGTGAAGGT
										GAGCAGGGC
										CTGGAGGCA
										GCTGGGAGG
										GC
chr	212154	C	G	MAP2	p.T273	0.005	0.002	1.78	2.05	AGATGGCCA	SEQ
17	98			K3	T	88	88	E-	[1.35-	TCCTGCGGT	ID
								03	3.11]	TCCCTTACG	NO:
										AGTCCTGGG	394
										GGAC[C/G]CC
										GTTCCAGCA
										GCTGAAGCA
										GGTGGTGGA
										GGAGCCGTC
										CC
chr	213186	G	A	KCNJ1	p.R6Q	0.012	0.002	2.45	4.42	AGCCAGGGT	SEQ
17	71			8		04	75	E-	[3.02-	CCCCCAACC	ID
								12	6.32]	CCCGGGATG	NO:
										ACCGCGGCC	395
										AGCC[G/A]G
										GCCAACCCC
										TACAGCATC
										GTGTCATCG
										GAGGAGGAC
										GGG
chr	213188	G	A	KCNJI	p.A58	0.017	0.000	4.39	49.8	CCGCTTCGT	SEQ
17	26			2	T	16	35	E-	[33.5	CAAGAAGAA	ID
								73	1-	TGGCCAGTG	NO:
									74.0	CAACATTGA	396
									1]	GTTC[G/A]CC
										AACATGGAC
										GAGAAGTCA
										CAGCGCTAC
										CTGGCTGAC
										AT
chr	213197	G	A	KCNJI	p.E380	0.010	0.000	9.65	31.5	GTTCCTGCT	SEQ
17	92			2	K	05	32	E-	6[20.	GCCCAGCGC	ID
								39	08-	CAACTCCTT	NO:
									49.6]	CTGCTACGA	397
										GAAC[G/A]A
										GCTGGCCTT
										CCTGAGCCG
										TGACGAGGA
										GGATGAGGC
										GGA
chr	275807	G	A	CRIB	p.G15	0.006	0.004	4.80	1.53	CCCCTCCTTG	SEQ
17	75			A1	9S	37	16	E-	[1.03-	CAAGCCATG	ID
								02	2.28]	GGCTGGTTC	NO:
										AACAACGAA	398
										GTC[G/A]GCT
										CCATGAAGA
										TACAAAGTG
										GGGCGTAAG
										TACAAAAAC
										A
chr	276138	T	C	NUFIP	p.T392	0.006	0.004	3.46	1.56	GCTGACATA	SEQ
17	38			2	A	37	10	E-	[1.05-	GGGACCTGG	ID
								02	2.32]	GATAAGCGA	NO:
										CTTGATGAT	399
										TGGG[T/C]CT
										GAGTTTCCC
										CGGTAGATG
										ATGAAGATG
										ATGAAGATG
										AA
chr	368296	A	C	C17orf	p.M35	0.020	0.000	2.25	Inf	GAATTTGAG	SEQ
17	76			96	8R	34	00	E-		GCCAGGGGG	ID
								80		CTCAGGGAC	NO:
										AGCGGGACC	400
										CCCC[A/C]TC
										TGCCACCTC
										CACAGCGGG
										TGGGCGGGC
										GGGGGCTTA
										GA
chr	389534	G	C	KRT28	p.P251	0.019	0.000	7.38	2199	CGCTCGCAT	SEQ
17	72				R	36	01	E-	.94[3	GTTGTTCAA	ID
								114	06.0	CAAAACCGC	NO:
									1-	GAGGTCTAC	401
									1581	CCCC[G/C]GG
									5.81]	GCCGCGTTC
										ATCTCCACG
										TTCACGTTG
										CCCCCAGCC
										GC
chr	391908	A	G	KRTA	p.S59S	0.006	0.000	1.98	Inf	GCTGGCAGC	SEQ
17	97			P1-3		86	00	E-		AGCTGGTCT	ID
								41		CACAGCAGC	No:
										TTGGCTGGC	402
										AGCA[A/G]CT
										GGAGCTGCA
										GGTCCCACT
										AGTTGAGAA
										GCTAGGAAA
										TC
chr	392743	C	T	KRTA	p.R66	0.005	0.000	3.87	143.	GCAGCTGGG	SEQ
17	71			P4-11	H	15	04	E-	18[4	GCGACAGCA	ID
								27	9.13-	GCTGGAGAT	No:
									417.	GCAGCATCT	403
									29]	GGGG[C/T]GG
										CAGCAGGTG
										GGCTGGCAG
										CACACAGAC
										TGGCAGCAC
										TG
chr	392744	T	A	KRTA	p.S48	0.015	0.000	1.04	Inf	TGGCAGCAC	SEQ
17	26			P4-11	C	20	00	E-		ACAGACTGG	ID
								90		CAGCACTGG	No:
										GGCCTGCAG	404
										CAGC[T/A]GG
										ACACACAGC
										AGCTGGGGC
										GACAGTAGG
										TGGTCCTGC
										AG
chr	392744	A	T	KRTA	p.C45	0.005	0.000	3.82	Inf	ACAGACTGG	SEQ
17	35			P4-11	S	64	00	E-		CAGCACTGG	ID
								34		GGCCTGCAG	No:
										CAGCTGGAC	405
										ACAC[A/T]GC
										AGCTGGGGC
										GACAGTAGG
										TGGTCCTGC
										AGCAGGTGG
										TC
chr	392744	C	T	KRTA	p.C44	0.005	0.000	3.08	Inf	AGACTGGCA	SEQ
17	37			P4-11	Y	15	00	E-		GCACTGGGG	ID
								31		CCTGCAGCA	No:
										GCTGGACAC	406
										ACAG[C/T]AG
										CTGGGGCGA
										CAGTAGGTG
										GTCCTGCAG
										CAGGTGGTC
										TC
chr	393166	C	T	KRTA	p.R107	0.011	0.000	4.62	Inf	AGCAGGTGG	SEQ
17	23			P4-4	R	52	00	E-		GCTGGCAGC	ID
								69		ACACAGACT	No:
										GGCAGCACT	407
										GGGG[C/T]CT
										GCAGCAGCT
										GGGGCGGCA
										GCAGGTGGT
										CCTACAGCA
										GG
chr	393462	A	C	KRTA	p.T21	0.005	0.000	6.33	577.	GCTGTCAGC	SEQ
17	01			P9-1	T	15	01	E-	37[7	CTACATGCT	ID
								30	7.65-	GCAGGACCA	No:
									4293	CCTGCTGCA	408
									.3]	GGAC[A/C]AC
										CTGCTGGAA
										GCCCACCAC
										TGTGACCAC
										CTGCAGCAG
										CA
chr	393465	A	C	KRTA	p.N14	0.024	0.000	2.06	Inf	TGCTGCCAG	SEQ
17	75			P9-1	6T	51	00	E-		CCTACCTGC	ID
								133		TGCCAGCCC	No:
										ACCTGCTGC	409
										AGGA[A/C]C
										ACCTCTTGC
										CAGCCCACC
										TGCTGTGGG
										TCCAGCTGC
										TGC
chr	422392	A	G	C17orf	p.S645	0.007	0.004	2.63	1.55	ACTCCTGAG	SEQ
17	92			53	G	11	60	E-	[1.06-	TGAGCTTCC	ID
								02	2.25]	TGAAGACTT	No:
										CTTCTGTGG	410
										GACC[A/G]GT
										AGTTGAGAC
										TGCCCCAAC
										GCAGGACAA
										CCCACCATG
										AG
chr	428829	G	A	GJC1	p.L71	0.008	0.004	3.63	1.74	CCACCAGGA	SEQ
17	73				L	09	66	E-	[1.22-	TGATCTGGA	ID
								03	2.48]	ACACCCAGA	No:
										AGCGTACAT	411
										GGGA[G/A]A
										GAGGTGCAA
										ACGCATCAT
										AACAGACAT
										TCTCACAGC
										CCG
chr	439234	C	T	SPPL2	p.L380	0.011	0.007	4.61	1.59	TGTGCGGCT	SEQ
17	10			C	L	27	13	E-	[1.18-	GCCCACTCT	ID
								03	2.14]	CAAGAACTG	No:
										CTCCTCCTTC	412
										CTG[C/T]TGG
										CCCTGCTGG
										CCTTTGATGT
										CTTCTTTGTC
										TTCGTCAC
chr	452145	A	C	CDC2	p.N57	0.022	0.000	2.16	Inf	ATACGACTT	SEQ
17	23			7	5K	55	00	E-		TGTCTTTGTA	ID
								134		CTTCATTACC	No:
										ACTTACCAT	413
										GC[A/C]TTAT
										AATGTCTAG
										GATTGACTC
										TGATAGCAT
										TTCGAAAAC
chr	452146	C	T	CDC2	p.A53	0.005	0.000	1.38	Inf	AGAGTATAG	SEQ
17	54			7	2T	88	00	E-		GCATAAGCG	ID
								35		TAATTTGGA	No:
										TCAACTTGG	414
										ATAG[C/T]TC
										TCTGGAAGA
										ATTTAATTG
										CAATATCAT
										GTTCCCGTT
										GC
chr	452146	T	C	CDC2	p.S517	0.015	0.000	3.52	Inf	TGGAAGAAT	SEQ
17	99			7	G	93	00	E-		TTAATTGCA	ID
								95		ATATCATGT	No:
										TCCCGTTGC	415
										AGAC[T/C]GA
										AACAGTTCC
										CTGCAGCAC
										ACCAGGCCT
										TAAAAAAAT
										GG
chr	452162	A	G	CDC2	p.Y47	0.008	0.000	1.83	Inf	GCCAAAGTG	SEQ
17	16			7	0Y	58	00	E-		TTGTAGAGT	ID
								51		AGATCTCCA	No:
										TGCCTTCAA	416
										CTCT[A/G]TA
										ATTCTCAAT
										CCTTCTAAC
										CTCTGAGAA
										TATTCTTTCA
										G
chr	452192	T	C	CDC2	p.Y43	0.015	0.000	2.76	Inf	ATAGGCCCT	SEQ
17	83			7	5C	93	00	E-		TCCAATTTG	ID
								95		GCACAGTAC	No:
										CCAACCAGT	417
										ATTG[T/C]AG
										TGGTGAGAA
										GGTAGATGG
										CTCAAAATA
										TTTATAGCTT
										C
chr	452292	A	G	CDC2	p.T266	0.028	0.000	3.43	1102	CTCGGCTAT	SEQ
17	61			7	T	92	03	E-	.44[3	TTCCACTCTG	ID
								167	50.3	TGAGAAGAC	No:
									6-	AGACTTTGT	418
									3468	TCC[A/G]GTT
									.91]	TGGCCGATT
										CTGGCAACA
										GACTGTAAA
										ACACGAAAA
										G
chr	452342	G	C	CDC2	p.L214	0.017	0.000	6.35	2015	AAAGTATCT	SEQ
17	98			7	V	89	01	E-	.93[2	TGTTTGACTT	ID
								105	80.1	ACCTTGGGG	No:
									3-	TTAATGGAC	419
									1450	TAA[G/C]AGC
									7.61]	TGCTGGTCC
										TCCTAATAA
										ACTTCGACC
										AGTTTTTGGT
chr	452493	T	G	CDC2	p.A54	0.005	0.000	1.90	32.6	TAGTACAAC	SEQ
17	72			7	A	64	17	E-	9[17.	TGTGTCCTTT	ID
								22	63-	CAAGAGTCT	No:
									60.6	ATATGCTTT	420
									2]	ATA[T/G]GCC
										TTTCCTGAG
										CGGTAATAA
										CAGGTTGCC
										AGTAAAAAC
										A
chr	486534	G	C	CACN	p.G54	0.010	0.000	1.36	Inf	CCACCACCC	SEQ
17	06			A1G	8A	05	00	E-		TCGACGCCT	ID
								53		GCCCTCTCC	No:
										GGGGCCCCC	421
										CCTG[G/C]TG
										GCGCAGAGT
										CTGTGCACA
										GCTTCTACC
										ATGCCGACT
										GC
chr	559172	G	A	MRPS	p.H14	0.012	0.007	1.02	1.65	CACTCAAGT	SEQ
17	91			23	2H	50	59	E-	[1.25-	GTTCGGATT	ID
								03	2.2]	TCCGGGAAA	No:
										CGTGACTAC	422
										CTCC[G/A]TG
										TTGCTTAAA
										AGACCAGAT
										TTAAGTATC
										ACAGAGATG
										TT
chr	560566	C	T	VEZF1	p.Q34	0.010	0.000	2.60	18.2	TCCCTGGCC	SEQ
17	07				8Q	29	57	E-	[12.1	AGCTTGTCA	ID
								32	3-	CATGTTGTT	NO:
									27.3	GTTGTTGTTG	423
									2]	TTG[C/T]TGC
										TGCTGCTGC
										TGCTGCTGC
										TGCTGCTGC
										TGCTGCTTTT
chr	615685	C	T	ACE	p.T342	0.009	0.006	1.34	1.52	CCCCAGTTT	SEQ
17	77				M	80	47	E-	[1.1-	GGGCAGAAC	ID
								02	2.09]	TCCCTCTGCT	No:
										TGCAGGGCT	424
										GGA[C/T]GCC
										CAGGAGGAT
										GTTTAAGGA
										GGCTGATGA
										TTTCTTCACC
chr	616837	T	C	TACO	p.H16	0.006	0.003	4.17	1.84	TATCTAACA	SEQ
17	83			1	6H	86	75	E-	[1.25-	GTAGCCACA	ID
								03	2.69]	AGTGCCAAG	No:
										CAGACATTA	425
										GACA[T/C]AT
										CCTGAATAA
										GAATGGGTA
										AGTGTGCGT
										CTGGGAGGA
										GT
chr	620386	T	C	SCN4A	p.H59	0.007	0.004	3.76	1.5[1	CACAGTGAG	SEQ
17	02				9R	11	73	E-	.03-	CACGTTGTC	ID
								02	2.19]	AAAGTGCTC	NO:
										CGTCATGGG	426
										GTAA[T/C]GT
										TCCATGGCC
										ATGAAGAGG
										GTGTTGAGC
										ACGATGCAG
										AT
chr	742881	G	A	QRIC	p.D72	0.009	0.000	2.53	1105	AACCAGGCT	SEQ
17	47			H2	1D	80	01	E-	.65[1	GATCTGCAC	ID
								57	51.9	CAGGTTGGA	NO:
									6-	TCAAACCAC	427
									8044	GCTG[G/A]TC
									.57]	CATTCCAGG
										TTGGACCAA
										ACCACGCTG
										ATCCACTCC
										AG
chr	742881	C	T	QRIC	p.R713	0.006	0.000	5.40	Inf	GATCAAACC	SEQ
17	72			H2	H	62	00	E-		ACGCTGGTC	ID
								40		CATTCCAGG	No:
										TTGGACCAA	428
										ACCA[C/T]GC
										TGATCCACT
										CCAGGTTGC
										ACCAAACCA
										CGCTGATCC
										AC
chr	742882	C	T	QRIC	p.R703	0.017	0.000	8.11	407	GACCAAACC	SEQ
17	02			H2	H	89	04	E-	[164.	ACGCTGATC	ID
								100	39-	CACTCCAGG	NO:
									1007	TTGCACCAA	429
									.67]	ACCA[C/T]GC
										TGATCCACT
										CCAGGTTGG
										ACCAAACCA
										CGCTGATCT
										GC
chr	742884	A	T	QRIC	p.V63	0.009	0.000	5.96	Inf	ACCACGCTG	SEQ
17	18			H2	1D	31	00	E-		AACTGCACC	ID
								56		AGGTTGCAC	NO:
										CAAACCACG	430
										CTGA[A/T]CT
										ATACCAGGT
										TGCACCAAA
										CTACGCTGA
										ACTTCACCA
										GG
chr	742885	C	T	QRIC	p.R572	0.007	0.000	1.92	799.	CAAACCACG	SEQ
17	95			H2	H	11	01	E-	67[1	CTGATGATC	ID
								41	08.9	TGCACGAGG	NO:
									1-	TTGTGCCAA	431
									5871	ACCA[C/T]GC
									.76]	TGATCTACT
										CCAGGTTGG
										ACCAAACCA
										TGCTGAACT
										GC
chr	743831	T	C	SPHK1	p.R285	0.005	0.002	1.15	1.82	GTCTGGGGG	SEQ
17	09				R	15	84	E-	[1.17-	AGATGCGCT	ID
								02	2.83]	TCACTCTGG	NO:
										GCACCTTCC	432
										TGCG[T/C]CT
										GGCAGCCCT
										GCGCACCTA
										CCGCGGCCG
										ACTGGCCTA
										CC
chr	768883	G	A	LOC10	p.G89	0.010	0.007	4.44	1.39	TCCACAGCT	SEQ
17	19			065351	G	78	79	E-	[1.02-	TGGCATCCG	ID
				5				02	1.9]	CTCTTCTCTG	NO:
										CAGAGCGAG	433
										ATC[G/A]CCT
										TTGCCCCGG
										GCTTGTAGC
										AATTTGTGC
										TTTTTCCTCC
chr	792545	C	T	SLC38	p.V16	0.006	0.003	1.29	1.72	CACTGCCCA	SEQ
17	30			A10	9M	37	72	E-	[1.15-	CTGAAGAGG	ID
								02	2.56]	CCGTGCTTG	NO:
										AGAGAGGAG	434
										AGCA[C/T]GA
										TCTGCAGAG
										GGAGAGGGG
										AGAGAGCAC
										GGGGCAGGT
										CA
chr	796820	T	C	SLC25	p.I57T	0.005	0.002	1.51	2.24	ATGACGGGC	SEQ
17	59			A10		15	31	E-	[1.43-	ATGGCGCTG	ID
								03	3.5]	CGGGTGGTG	NO:
										CGTACCGAC	435
										GGCA[T/C]CC
										TGGCACTCT
										ACAGCGGCC
										TGAGCGCCT
										CGCTGTGCA
										GA
798471	chr	G	A	ALYRE	p.R148	0.005	0.003	1.10	1.78	GCTCAAAGT	SEQ
17	52			F	R	64	17	E-	[1.17-	GCACGTCTG	ID
								02	2.72]	CTGTTCCTA	NO:
										AGCTGCGAC	436
										CAGA[G/A]C
										GATCATAGT
										GCACAGCCG
										CCTTCTTCAG
										CGTTCCAAA
										TT
chr	799545	G	A	ASPSC	p.L252	0.018	0.000	1.09	2063	CTGCCCCCTT	SEQ
17	45			R1	L	38	01	E-	.13[2	TGTTCCTTTC	ID
								107	86.7	TCGGGTGGG	NO:
									9-	GGACAGAGA	437
									1484	CT[G/A]GGGG
									2.01]	GCCCTCCTG
										GGCCCACGA
										GGCCTCTGA
										CATCATCTT
chr	805296	G	T	FOXK	p.P259	0.009	0.006	1.23	1.55	GTTTTGTGTT	SEQ
17	14			2	P	80	35	E-	[1.12-	TGTTTTTTAA	ID
								02	2.14]	ATACAGGAT	No:
										GATTCAAAG	438
										CC[G/T]CCTT
										ACTCCTACG
										CGCAGCTGA
										TAGTTCAGG
										CGATTACGA
chr	808993	T	C	TBCD	p.L118	0.011	0.006	3.07	1.62	AACCGTCTG	SEQ
17	49				5P	27	98	E-	[1.2-	TGTGACCTT	ID
								03	2.19]	CTGGGCGTA	No:
										CCCAGGCCC	439
										CAGC[T/C]GG
										TGCCCCAGG
										TAACCCTGT
										CACCTTCAC
										AGCATGAGG
										TG
chr	345222	T	C	TGIF1	p.P82P	0.006	0.000	1.05	9.21	CGACCCCCT	SEQ
18	3					13	67	E-	[5.81-	CTGCGCTCC	ID
								14	14.5	TGGGGTCCT	No:
									91]	CCTGCGCCC	440
										CCCC[T/C]CC
										TCCACCGGC
										GCGCTGCCC
										ACAGCCGCG
										TGCCCTCTCC
										C
chr	939652	C	T	TWSG	p.A15	0.006	0.003	4.36	1.54	CACCACCAG	SEQ
18	4			1	7V	13	99	E-	[1.03-	AATGTGTCT	ID
								02	2.31]	GTCCCCAGC	No:
										AATAATGTT	441
										CACG[C/T]GC
										CTTATTCCA
										GTGACAAAG
										GTAACTGCC
										AACAGTTGA
										CT
chr	988737	C	A	TXND	p.L232	0.010	0.000	4.36	99.4	CAAGTCCCC	SEQ
18	1			C2	I	29	10	E-	4[49.	AGAAGAAGC	ID
								49	86-	CATCCAGCC	No:
									198.	CAAGGAGGG	442
									331]	TGAC[C/A]TC
										CCCAAGTCC
										CTAGAGGAA
										GCCATCCAG
										CCCAAGGAG
										GG
chr	125467	A	G	SPIRE	p.A46	0.005	0.002	1.16	1.82	CTTCTTCTGC	SEQ
18	78			1	A	15	84	E-	[1.17-	AGCCTCATA	ID
								02	2.83]	GCCCTCATC	No:
										ATTGCTACC	443
										GTC[A/G]GCT
										TCCACCGTG
										TTGGCCATG
										TGATCGATA
										AGCTGCTCT
										A
chr	189642	G	A	GREB	p.E93	0.007	0.004	1.32	1.65	CAATCTAAC	SEQ
18	86			1L	K	60	61	E-	[1.14-	AGTTAATGA	ID
								02	2.4]	AATGGAAGA	No:
										TGATGAAGA	444
										CGAT[G/A]AA
										GAAATGTCT
										GATTCAAAC
										AGCCCACCA
										ATTCCCTATT
										C
chr	289343	A	G	DSG1	p.I739	0.011	0.007	8.43	1.54	TGTAGGTTC	SEQ
18	74				V	03	18	E-	[1.14-	CCCTGCTGG	ID
								03	2.09]	CTCTGTGGG	No:
										TTGTTGTAG	445
										CTTC[A/G]TT
										GGAGAAGAC
										CTGGATGAC
										AGCTTCTTG
										GATACCCTG
										GG
chr	337850	G	A	MOCO	p.Q35	0.012	0.009	1.86	1.42	GAATGGAGA	SEQ
18	83			S	4Q	75	01	E-	[1.07-	ATATAAAGC	ID
								02	1.88]	AGCACACCT	No:
										TCACCTTGG	446
										CTCA[G/A]TA
										TACCTACGT
										GGCCCTGTC
										CTCTCTCCA
										GTACCCCAA
										TG
chr	641789	C	A	CDH1	p.V48	0.005	0.000	1.39	618.	ATGGATTCA	SEQ
18	22			9	7L	88	01	E-	95[8	TCTCTATCCA	ID
								33	3.71-	CTGCACTGA	No:
									4576	TAGTCTGAA	447
									.34]	TTA[C/A]CTA
										AAAAAAAAG
										GGGGATAGA
										TTTTTGTTGT
										TGTTTGGAT
chr	721140	G	A	FAM6	p.A22	0.006	0.003	1.29	1.75	TGCCCTGTG	SEQ
18	55			9C	1V	62	79	E-	[1.16-	GTGGGGGCT	ID
								02	2.65]	GCCCGCGGC	No:
										CAGGAACTC	448
										CACC[G/A]CG
										TAGAAGTGG
										CCGCAGGAA
										CCCAGCACG
										GGCAGCACG
										TG
chr	723467	T	C	ZNF40	p.G12	0.008	0.005	1.66	1.56	ATTGTGAGG	SEQ
18	01			7	42G	33	35	E-	[1.1-	GTGAAGGAG	ID
								02	2.21]	GAAACGCAG	No:
										GAGACGGTG	449
										GAGG[T/C]GT
										TGTCCCCCA
										CAGACACCT
										GTGCCCTGT
										GACGCTCGA
										TG
chr	287703	G	A	PPAP2	p.R85	0.010	0.006	9.91	1.53	ACCTTGTAT	SEQ
19				C	C	54	93	E-	[1.12-	ACAGCAGCC	ID
								03	2.08]	ACGTAGTTG	No:
										TTGAAGTCC	450
										GAGC[G/A]A
										GAATAGAGC
										CGGTCTGTG
										TACACCAGG
										TAGGCTTCC
										CCG
chr	474688	T	G	ODF3	p.R20	0.012	0.006	1.39	1.85	ACTTCCTCA	SEQ
19				L2	R	25	67	E-	[1.38-	GGCCGGTCT	ID
								04	2.47]	CCGGAATCT	No:
										GGCCCTCCG	451
										TCAC[T/G]CG
										CCGGCCAAG
										GGGGGCTGT
										GGCCAGCCG
										TGGGGTGGA
										GT
chr	104374	C	T	ABCA7	p.L318	0.005	0.003	1.35	1.79	GGGGGTGCT	SEQ
19	7				L	39	01	E-	[1.16-	GTCCACAGG	ID
								02	2.76]	TGAACCGGA	No:
										CCTTCGAGG	452
										AGCT[C/T]AC
										CCTGCTGAG
										GGATGTCCG
										GGAGGTGTG
										GGAGATGCT
										GG
chr	143033	C	T	DAZA	p.F280	0.007	0.000	5.26	Inf	TGTCCACCC	SEQ
19	0			P1	F	11	00	E-		CTCCTGGAG	ID
								40		GCTTTCCCCC	No:
										TCCCCAGGG	453
										CTT[C/T]CCT
										CAGGGCTAC
										GGTGCCCCG
										CCACAGTTC
										AGTAAGTCT
										A
chr	145711	C	A	APC2	p.P359	0.029	0.000	8.67	2568	CGCGCCAAC	SEQ
19	1				Q	90	01	E-	.75[3	GCGGCGCTG	ID
								162	58.8	CACAACATC	No:
									6-	GTCTTCTCGC	454
									1838	AGC[C/A]GG
									7.26]	ACCAGGGCC
										TGGCGCGCA
										AGGAGATGC
										GCGTCCTGC
										AC
chr	162098	G	T	TCF3	p.P360	0.015	0.000	1.11	103.	TCCCCTCCCC	SEQ
19	0				P	20	15	E-	81[5	CCAAAACCC	ID
								64	1.56-	TCACAGACC	No:
									209.	TGCCAGGCC	455
									02]	CTG[G/T]GGG
										GAGCCCACG
										GGGGTAGAA
										GGGCTGGAC
										GAGAAGTTA
										T
chr	177540	C	G	ONEC	p.G48	0.006	0.000	1.74	Inf	TGAACCGCT	SEQ
19	8			UT3	3G	13	00	E-		GGGCTGAGG	ID
								27		AGCCCAGCA	NO:
										CGGCCCCCG	456
										GGGG[C/G]CC
										CGCCGGCGC
										CACGGCCAC
										TTTCTCCAA
										GGCCTGAGG
										CG
chr	224844	A	G	SF3A2	p.N43	0.012	0.000	3.76	Inf	CCTGGGGTC	SEQ
19	5				2S	25	00	E-		CACCCTCAG	ID
								47		CCTCCGGGA	NO:
										GTTCACCCC	457
										TCAA[A/G]TC
										CTGGGGTGC
										ACCCCCCAA
										CTCCCATGC
										CCCCAATGC
										TG
chr	225042	A	G	ANIH	p.Y16	0.007	0.000	2.29	171.	GGAGGAGCT	SEQ
19	3				7C	84	05	E-	42[5	GGCCCCCCA	ID
								36	2.47-	GAGCTGGCG	NO:
									560.	CTGCTGGTG	458
									02]	CTGT[A/G]CC
										CTGGGCCTG
										GCCCTGAGG
										TCACTGTGA
										CGAGGGCTG
										GG
chr	287732	C	T	ZNF55	p.R122	0.008	0.005	4.26	1.46	AAGGGTGGA	SEQ
19	0			6	C	09	57	E-	[1.02-	GAGACCATG	ID
								02	2.07]	TAAAAGCAG	NO:
										TAAAGGTAA	459
										TAAA[C/T]GT
										GGAAGAACC
										TTCAGAAAG
										ACTCGAAAT
										TGTAATCGT
										CA
chr	395944	G	A	DAPK	p.R340	0.007	0.005	2.43	1.55	CCACGTCCT	SEQ
19	4			3	R	84	07	E-	[1.08-	CGTGGCAGA	ID
								02	2.24]	GCCGCCGGC	NO:
										TGCGCTGCA	460
										GCTC[G/A]CG
										CAGGCCCTC
										CTCGGCGGC
										CGCCGCCTC
										CTCCAGCAC
										CT
chr	451121	C	G	PLIN4	p.S906	0.007	0.000	3.99	Inf	ACTGCAGAC	SEQ
19	3				T	84	00	E-		GGTGTCCTT	ID
								45		GGTACCGGT	NO:
										CAGGACAGT	461
										CTTG[C/G]TG
										GTGTCCACG
										CCGGTCTGG
										ACAGTCCCT
										TTGGCCAAG
										TT
chr	451351	C	T	PLIN4	p.K13	0.006	0.000	1.43	681.	GGACAGCCT	SEQ
19	9				7K	13	01	E-	44[9	TCGAGGTGT	ID
								35	2.31-	CCAGACCCC	No:
									5030	CTTGGACGG	462
									.26]	CCCC[C/T]TT
										AGCCATGTC
										CATGGCCCC
										TGTGACCCC
										GCTGGACAC
										CA
chr	572022	C	T	LONP	NM_	0.012	not	2.62	Inf	CGCCGCGAA	SEQ
19	9			1	001276480:	76	found	E-		ACGCACGTG	ID
					c.-			24		ACGCCCGGC	No:
					160 + 1					GCGTGCCTC	463
					G > A					GGTA[C/T]CC
										GATGGGCGC
										GTGGCTCGA
										AACAGCCGC
										TTCAGGGAG
										CT
chr	583160	G	A	FUT6	p.T324	0.009	0.006	1.69	1.5[1	GCAGAAAGC	SEQ
19	8				M	56	38	E-	.09-	GAGTGCCCA	ID
								02	2.08]	GCTGAAGGA	No:
										GCGAGGCCG	464
										CAGC[G/A]TC
										TCCCGCCAG
										CGAAAGTAG
										CTCAGGTAG
										CGGGCGTGG
										TC
chr	813810	C	T	FBN3	p.V25	0.007	0.004	9.73	1.66	CCCCCGAGG	SEQ
19	4				94I	60	59	E-	[1.15-	GCCTGATCA	ID
								03	2.39]	AAGTCAAAG	No:
										CCAGAGGGG	465
										CAGA[C/T]GC
										AGCGGAAGC
										CACCAAGAG
										TGTTGCGAC
										AGGAGGCGC
										TC
chr	815480	G	A	FBN3	p.P207	0.006	0.000	1.44	Inf	TGGGTGAGG	SEQ
19	2				6S	86	00	E-		GGCTCACCT	ID
								40		TCTCGGGAG	No:
										TCATCCGGG	466
										CCTG[G/A]GA
										CTGCCCCGT
										GGCCAAAGG
										GGCAGAGCT
										CCTGAAAGG
										CA
chr	837316	C	T	CD320	p.G4D	0.006	0.003	2.31	1.77	CAGAGCCCC	SEQ
19	4					51	69	E-	[1.07-	TGTTCGCCA	ID
								02	2.78]	CGCTCCAAC	No:
										CTGCGCCAT	467
										CCAA[C/T]CG
										CCGCTCATG
										CTGTCCCCA
										CAGCGGCGC
										CGGCCACGC
										GC
chr	839896	A	G	KANK	p.D48	0.022	0.000	1.53	Inf	AGCTACCCG	SEQ
19	1			3	9D	30	00	E-		GGGGCTCGG	ID
								101		CGCCACCGT	No:
										TCTCGCTGTC	468
										GCC[A/G]TCG
										CTGTCGCTG
										GCGTCCTCG
										CTGGAGGAG
										CTCTCGTAC
										C
chr	856436	G	T	PRAM	p.P109	0.006	0.000	1.85	373.	CAGTTTGGA	SEQ
19	6			1	Q	86	02	E-	54[8	CGGCTTCTT	ID
								38	8.96-	GGGGAGGTC	No:
									1568	AGTGACCTC	469
									.57]	AGGC[G/T]GC
										GGGGGCTTC
										TTGGGGAGG
										TCAGTGACC
										TCAGGCGGC
										GG
chr	905982	A	G	MUC1	p.S920	0.013	0.009	9.32	1.47	GTATCTGTA	SEQ
19	7			6	7P	24	05	E-	[1.11-	GTGACTTCA	ID
								03	1.93]	GTGATGGCC	No:
										AGTATTTCA	470
										GCTG[A/G]GG
										TGCTGCTCA
										AATTTGGGG
										GTGAACTGG
										TTTCAGGTTC
										T
chr	907288	G	C	MUC1	p.P485	0.005	0.003	4.88	1.54	ATGGTGGAG	SEQ
19	6			6	4A	64	66	E-	[1.01-	GTGGTAACA	ID
								02	2.35]	TTTGGAGAT	No:
										GTGACTTTA	471
										GATG[G/C]CT
										CTGGGTAAG
										CTGAGACAG
										TAGAATGTG
										ATTCAAATG
										CT
chr	923755	G	A	OR7G	p.P25S	0.008	0.004	1.80	1.67	GTGGCCAGG	SEQ
19	4			3		133	873	E-	[1.07-	TACATGGAC	ID
								02	2.5]	AGGAACAGC	No:
										ATGAAGAGG	472
										ATGG[G/A]CT
										GCAGCTCCG
										GATCCCCTG
										ACAATCCCA
										AGAGAAAGA
										AT
chr	114887	G	A	EPOR	p.P488	0.005	0.003	2.60	1.66	GGCAGAGGC	SEQ
19	25				S	39	25	E-	[1.08-	TCAGCGGCT	ID
								02	2.56]	GGGATAAGG	No:
										CTGTTCTCAT	473
										AAG[G/A]GTT
										GGAGTAGGG
										GCCATCGGA
										TAAGCCCCC
										TTGGGCTCC
										C
chr	120606	A	G	ZNF70	p.Q59	0.005	0.000	4.11	6.32	AAAGGACTC	SEQ
19	27			0	6Q	15	82	E-	[3.93-	ACACTGGAG	ID
								10	10.1	AGAAACCCT	NO:
									6]	ATGAGTGTA	474
										AGCA[A/G]TG
										TGGGAAAGC
										CTTCAGTTGT
										GCCTCAAAC
										CTTCGAAAG
										C
chr	121556	A	G	ZNF87	p.C173	0.007	0.000	2.32	Inf	GAACAGAAC	SEQ
19	97			8	C	35	00	E-		TGGGAAAAC	ID
								44		TGAATGCTT	NO:
										TCCCACACT	475
										GCTT[A/G]CA
										TTCATAGGG
										TTTTTTTGCA
										GAGTGGATT
										CTTTCATGTC
chr	125014	C	T	ZNF79	p.P587	0.005	0.000	1.69	115.	TGAGAGAAG	SEQ
19	51			9	P	15	04	E-	34[4	CAAATGCTT	ID
								26	3.47-	TCCCACATT	No:
									306.	CCTTACATTC	476
									02]	ATA[C/T]GGG
										TTCTCTCCAG
										TATGAGTTTT
										TTCATGTCCT
										TGAAGAA
chr	125411	C	T	ZNF44	p.P615	0.013	0.000	1.75	1489	TGAGAGAAG	SEQ
19	41			3	P	24	01	E-	.83[2	CAAATGCTT	ID
								77	06.0	TCCCACATT	NO:
									5-	CCTTACATTC	477
									1077	ATA[C/T]GGG
									1.89]	TTCTCTCCAG
										TATGAGTTTT
										TTCATGTCCT
										TGAAGAA
chr	141045	G	C	RFX1	p.P34	0.006	0.000	9.57	Inf	GCAGCGGTG	SEQ
19	56				A	37	00	E-		GGTGGCTGC	ID
								37		GGGGGCTGG	NO:
										GGTGCCGCT	478
										GGGG[G/C]TG
										GTGGCGGTG
										GCGGCTGGG
										GCTGGGCTT
										GTGGCGGGG
										CC
chr	153539	G	A	BRD4	p.P982	0.017	0.000	8.48	Inf	CGTGGAGGG	SEQ
19	36				S	65	00	E-		GGCTGATGC	ID
								60		TGCTGCTGG	NO:
										GGTGGAGGC	479
										TGGG[G/A]CT
										GGGGTGGTG
										GGGGTGGTG
										GCGGCTGCT
										GCTGCAGCT
										GC
chr	162756	C	T	CIB3	p.G13	0.007	0.000	3.10	88.1	ACCTTCTCA	SEQ
19	56				9R	84	09	E-	6[43.	CATACCAGG	ID
								38	31-	CTCACCTCCT	No:
									179.	CGGCACTCA	480
									45]	GCC[C/T]CCC
										CCGCGTCAG
										TTTGGTCAC
										CGTCTGCTC
										CAGGTCCCA
										C
chr	170390	A	C	CPAM	p.S110	0.005	0.003	2.24	1.67	GGCCTCGGG	SEQ
19	23			D8	3A	88	53	E-	[1.11-	AGGGTCCAG	ID
								02	2.53]	GCCACAATG	No:
										ACAGACTCA	481
										TTGG[A/C]TG
										GCTCTGGAC
										CATGGCCAA
										CCTGGAAAA
										AGAAACCAA
										GG
chr	178816	G	A	FCHO	p.R186	0.009	0.006	4.21	1.41	GAGAGCCTG	SEQ
19	68			1	Q	56	78	E-	[1.02-	CGGCGCTCA	ID
								02	1.95]	GTGGAAAAA	No:
										TACAACTCA	482
										GCCC[G/A]AG
										CTGACTTTG
										AGCAGAAGA
										TGCTGGACT
										CAGCCCTGG
										TA
chr	178889	A	G	FCHO	p.E423	0.006	0.004	4.13	1.51	AGAAGCAGC	SEQ
19	54			1	G	62	38	E-	[1.03-	CCTCTTGGC	ID
								02	2.23]	CTCACCCTCT	No:
										CTAGCTGTG	483
										CAG[A/G]GA
										GATTGCAGT
										CAGAGGAGC
										AGGTGTCCA
										AGAACCTCT
										TT
chr	197446	C	T	GAWP	p.E795	0.009	0.005	8.03	1.61	AGGCCCTCT	SEQ
19	14				K	07	65	E-	[1.15-	CCATAGCTG	ID
								03	2.26]	TGGGCCCAG	No:
										TGGGTTCTT	484
										ACCT[C/T]GG
										TAGGTGTGG
										CCGTGGGAT
										GCTGCTCCA
										GGGTACTGT
										GG
chr	202294	C	A	ZNF90	p.G34	0.018	0.000	3.39	Inf	TCCATACTG	SEQ
19	04				7G	14	00	E-		GAGAGAAAC	ID
								108		CCTACAAAT	No:
										GTGAAGAAT	485
										GTGG[C/A]AA
										AGCCTTCAG
										GCGCTCCTT
										AGTCCTTCG
										TACACATAA
										GA
chr	202295	C	A	ZNF90	p.G40	0.008	0.000	2.64	Inf	GTCATAGTG	SEQ
19	72				3G	82	00	E-		AAAAGAAAC	ID
								52		CCTACAAAT	No:
										GTGAAGAAT	486
										GTGG[C/A]AA
										AGCCTTCAA
										GCGCTCCTC
										AACACTTAC
										TATACATAA
										GA
chr	212400	T	C	ZNF43	p.F298	0.011	0.000	4.36	Inf	TGGAGAGAA	SEQ
19	06			0	L	03	00	E-		ACCCTACAG	ID
								66		ATGTGAAGA	No:
										ATGTGGCAA	487
										AACC[T/C]TT
										AACCGGTCC
										TCACACCTT
										ACTACACAT
										AAAAGAATT
										CA
chr	217194	T	A	ZNF42	p.H19	0.010	0.007	3.83	1.41	TTTGCATGCT	SEQ
19	40			9	5Q	05	15	E-	[1.03-	TTCACAACT	ID
								02	1.93]	AACTCAACA	No:
										TAAGAAAAT	488
										TCA[T/A]ATT
										AGAGAGAAT
										ACCTACAGA
										TGTAAAGAA
										TTTGGCAAT
										G
chr	221543	A	C	ZNF20	p.V11	0.024	0.000	1.90	Inf	AAAGCCTTT	SEQ
19	42			8	65G	02	00	E-		GCCACATTC	ID
								142		TTCACATTTG	No:
										TAGGGTTTC	489
										TCT[A/C]CAG
										TATGAATTTT
										CTTATGATA
										ACTAAGGGT
										TGAGGACCA
chr	221548	A	T	ZNF20	p.C100	0.005	0.003	4.87	1.54	AGGTTTGAT	SEQ
19	29			8	3S	64	66	E-	[1.01-	GACCAGTTG	ID
								02	2.35]	AAAGCTTTG	No:
										CCACATTCTT	490
										CAC[A/T]TTT
										GTAGGGTTT
										CTCTCCAGT
										ATGAATTAC
										CTTATGTTTA
chr	221556	A	G	ZNF20	p.H71	0.017	0.000	2.21	1917	TTTTGCCAC	SEQ
19	91			8	5H	65	01	E-	.14[2	ATTCTTCAC	ID
								102	66.3	ATTTGTAGG	No:
									5-	GTTTCTCTCC	491
									1379	AGT[A/G]TGA
									9.28]	ATTCTCTTAT
										GTTCCATAA
										GGTTTGAGG
										ACCAGTTGA
chr	222719	G	A	ZNF25	p.E456	0.014	0.000	6.24	Inf	GTCTTCATA	SEQ
19	18			7	K	71	00	E-		CCTTATTCG	ID
								88		ACATAAGAT	No:
										AATTCATAC	492
										TGGA[G/A]A
										GAAACCCTA
										CAAATGTGA
										AGAGTGTGG
										CAAAGCCTT
										TAA
chr	222720	A	G	ZNF25	p.I507	0.016	0.000	8.46	926.	CAAAGCCTT	SEQ
19	71			7	V	42	02	E-	98[2	TAACCGGTC	ID
								95	27.0	TTCACACCTT	No:
									4-	TCTCAACAT	493
									3784	AAG[A/G]TA
									.7]	ATTCATACT
										GGAGAGAAA
										CCCTACAAA
										TGTGAAGAA
										TG
chr	228476	G	A	ZNF49	p.K39	0.008	0.000	2.33	Inf	CACACCTTA	SEQ
19	44			2	1K	09	00	E-		CTACACATA	ID
								48		AGAGAATTC	No:
										ATACTGGAG	494
										AGAA[G/A]C
										CCTACAAAT
										GTGAAGAAT
										GTGGCAAAG
										CTTTTAACCT
										AT
chr	351753	G	A	ZNF30	p.D12	0.008	0.004	4.44	1.71	ATTTTCAAA	SEQ
19	06			2	2N	33	89	E-	[1.21-	TTCTAATAA	ID
								03	2.42]	GAATTTGGA	No:
										ATATACAGA	495
										ATGC[G/A]AC
										ACATTTAGA
										AGCACCTTT
										CATTCAAAG
										TCTACTCTTT
										C
chr	360024	T	C	DMKN	p.S276	0.006	0.001	1.79	6.01	CTGCCACCA	SEQ
19	05				G	37	07	E-	[3.87-	CTGCTGCCG	ID
								11	9.32]	CCACTGCTG	No:
										CCGCCACTG	496
										CTGC[T/C]GC
										CACTGCTGC
										TGCCACCAC
										TGCTGCTGC
										CATTGTTGTT
										G
chr	383774	C	T	WDR8	p.E229	0.009	0.000	5.77	Inf	CCTCCTCCTT	SEQ
19	17			7	8E	07	00	E-		CCTTTCCTCC	ID
								42		TCCTCCTCCC	No:
										TTACCTCCTC	497
										[C/T]TCCTCC
										CTTTCCTCTT
										CTTCCTCCCT
										TTCCTCCTCC
										TCCT
chr	383792	C	T	WDR8	p.A16	0.005	0.003	8.94	1.86	ATTTCTTGGC	SEQ
19	29			7	94A	64	03	E-	[1.21-	CAGTTTCTTC	ID
								03	2.88]	CTTTTCTGGG	NO:
										CCAATTTCTC	498
										[C/T]GCCTCC
										TGGCTTAGC
										TTCTCCCCTC
										TTTGGGCCA
										GTGTTT
chr	388172	G	A	KCNK	KCNK6	0.006	0.000	1.69	108.	AAAAGAAAA	SEQ
19	32			6	(NM_	86	06	E-	13[4	AGATTTACC	ID
					004823:			34	7.2-	CTTTACTCTC	No:
					exon2:				247.	TTTACTCCCC	499
					c.3				68]	TA[G/A]GCTA
					23-					TGGGTACAC
					1G > A)					AACGCCACT
										GACTGATGC
										GGGCAAGGC
chr	404084	G	A	FCGB	p.S147	0.006	0.000	6.61	702.	AATCTTTCA	SEQ
19	20			P	3S	37	01	E-	38[9	AGGGACCCT	ID
								37	5.29-	GGGGATCCA	NO:
									5177	CCAGCTTGT	500
									.19]	GGCA[G/A]G
										AGGACAGTG
										GCCCTGTGG
										GGCTGGAGA
										GGAGCCCAC
										AGA
chr	404086	T	A	FCGB	p.Q13	0.006	0.003	8.36	2.11	CTTGGGGTC	SEQ
19	85			P	85L	37	03	E-	[1.41-	GCCGTTGTA	ID
								04	3.15]	GTTCCCACA	NO:
										CAGGCCACA	501
										CATC[T/A]GC
										TGGTAGTAG
										TTTCCGGGG
										ACGGTGACC
										CGCACATAG
										TA
chr	405805	A	T	ZNF78	p.C615	0.006	0.004	2.82	1.57	AGCTGGGTG	SEQ
19	06			0A	S	62	24	E-	[1.06-	GGAAGACTA	ID
								02	2.31]	AAAACCTTT	NO:
										CCACATTCC	502
										TTAC[A/T]TT
										CAAAGGGTT
										TCTCACCAG
										TATGCAATT
										TCTGATGTC
										GA
chr	413558	A	G	CYP2A	p.L73	0.005	0.002	1.18	2.55	GCATCATGT	SEQ
19	49			6	L	88	32	E-	[1.67-	CCACACAGC	ID
								04	3.88]	ACCACGACC	NO:
										CGCCGGGGC	503
										CCCA[A/G]GT
										GAATGGTGA
										ACACGGGGC
										CATAGCGCT
										CACTGATCT
										GA
chr	416339	A	G	CYP2F	p.P472	0.008	0.004	1.79	1.84	TGCAGCCGC	SEQ
19	27			1	P	09	41	E-	+[1.29-	TGGGTGCGC	ID
								03	2.62]	CCGAGGACA	No:
										TCGACCTGA	504
										CCCC[A/G]CT
										CAGCTCAGG
										TCTTGGCAA
										TTTGCCGCG
										GCCTTTCCA
										GC
chr	428553	C	T	MEGF	p.P847	0.009	0.000	3.25	Inf	TGGGGTTCT	SEQ
19	73			8	P	31	00	E-		GACTCCTCT	ID
								47		GCCCAACTG	No:
										ACCCCCAGG	505
										ACCC[C/T]TT
										CTGTGAGTG
										GCATCAGAG
										CACCAGCCG
										CAAAGGGGA
										CG
chr	434117	C	T	PSG6	p.L325	0.005	0.001	8.18	3.69	CTGGCCCAC	SEQ
19	38				L	39	47	E-	[2.36-	AGAGGAACA	ID
								07	5.76]	AAGGATACT	No:
										CACAGAGGA	506
										CATT[C/T]AG
										GGTGACTGG
										GTTACTGCG
										GATGCCACC
										ATATCGGTC
										CC
chr	434117	G	A	PSG6	p.T324	0.005	0.001	2.40	4.64	CCCACAGAG	SEQ
19	42				I	39	17	E-	[2.95-	GAACAAAGG	ID
								08	7.29]	ATACTCACA	No:
										GAGGACATT	507
										CAGG[G/A]TG
										ACTGGGTTA
										CTGCGGATG
										CCACCATAT
										CGGTCCCGT
										AT
chr	440651	C	T	XRCC	p.E50	0.006	0.004	2.90	1.56	CATCATTCC	SEQ
19	67			1	E	62	26	E-	[1.06-	CAATGTCCA	ID
								02	2.3]	CACTGTGTA	No:
										TCTGCTCCTC	508
										CTT[C/T]TCC
										AACTGTGGG
										CAGAGAGAG
										AGGCCACTG
										TCAGTGCCT
										G
chr	445006	A	T	ZNF15	p.Q22	0.005	0.002	1.84	1.76	GGCAAGGAA	SEQ
19	77			5	3L	15	93	E-	[1.13-	TTTAGTCAA	ID
								02	2.74]	AGCTCACAT	No:
										CTGCAAACT	509
										CATC[A/T]GA
										GAGTCCACA
										CTGGAGAGA
										AACCATTCA
										AATGTGAGC
										AA
chr	448906	A	G	ZNF28	p.L578	0.008	0.005	1.46	1.57	TTATAATGTT	SEQ
19	74			5	P	82	64	E-	[1.12-	TCTCTCTGCT	ID
								02	2.2]	CATGTAGTC	No:
										TTTGATGAG	510
										TC[A/G]GAAG
										GTCCTTTCCA
										CGCTCACAA
										TGTGTGTAC
										TGTGTCTC
chr	458987	A	G	PPP1R	p.P435	0.008	0.000	1.83	26.8	CAGGGGGCC	SEQ
19	43			13L	P	33	31	E-	[12.4-	ATGTCTGTT	ID
								22	57.9	GGGGATGCT	No:
									3]	GGGGGGCTG	511
										GGGT[A/G]G
										GGGTTTGGG
										GTTGGGTCT
										GGGGCTGTG
										GGGGCAGCT
										GGG
chr	461377	G	A	EML2	p.R213	0.006	0.000	1.59	Inf	TCCCCGGTG	SEQ
19	13				X	62	00	E-		GGCAGCAAA	ID
								39		TAAAGGTTG	No:
										GCCCGGCAG	512
										TCTC[G/A]GC
										CACGGTAGC
										CATAGCTGG
										AGCCACCCA
										GGGGCTGGT
										TA
chr	462154	G	C	FBXO	p.P420	0.005	0.000	3.35	595.	GCCGGGCGC	SEQ
19	95			46	R	88	01	E-	7[80.	AGTGGCCGG	ID
								33	57-	GGAGTCGGC	No:
									4404	CGGGGGTGG	513
									.4[	CTCC[G/C]GG
										GGCCCGTCC
										GGCCCGCGG
										TTCTGGAGA
										AAGAAGAGC
										TG
chr	463139	C	G	RSPH6	p.A27	0.006	0.003	3.10	1.58	CCTGTTCGC	SEQ
19	18			A	7A	13	90	E-	+[1.05-	CTTCAGTGC	ID
								02	2.36]	CGCCTCCAC	No:
										TCCGGGTGA	514
										ACAG[C/G]GC
										CTTCTGTTTC
										TCCGCCATC
										TTGTAGGTG
										GGCTGCATC
										T
chr	472042	C	T	PRKD	p.V32	0.011	0.008	4.45	1.36	TTGTCAGCC	SEQ
19	07			2	4M	27	30	E-	[1.01-	TCGCTGAAA	ID
								02	1.83]	TCGGTGGCC	No:
										TCCTCCATC	515
										GGCA[C/T]AT
										CTGTGGGGA
										CGGAGGCAT
										CAGAGGGGT
										CTCCACCCA
										GT
chr	475752	A	G	ZC3H4	p.H62	0.005	0.002	4.03	2.49	CAGGGTGCA	SEQ
19	94				9H	15	07	E-	[1.58-	TGTCCGGGT	ID
								04	3.93]	GCATGTCGG	No:
										GGTGCATGT	516
										CAGG[A/G]TG
										CATTGGACC
										GCCCATTGG
										CCCTGGGGG
										TCCCATGTT
										GG
chr	486245	C	T	LIG1	p.V68	0.013	0.009	1.28	1.44	AGGTAGGCG	SEQ
19	55				5M	24	24	E-	[1.09-	CCGATCACC	ID
								02	1.89]	ACCAGGTCC	No:
										AGGGTGTCA	517
										CCCA[C/T]GC
										CATCAAGGT
										AGTCCTTCTT
										CAGCTGGGA
										GAAGGGGAG
										G
chr	486433	G	A	LIG1	p.L304	0.005	0.002	1.28	1.97	CCAAGCTCC	SEQ
19	12				F	21	65	E-	[1.11-	AGGCCCTGC	ID
								02	3.26]	TGGGGTGGC	No:
										CCAAGGTGG	518
										TTGA[G/A]GC
										TGAGGTAGA
										GGACAGGGA
										GGAGGTCTG
										GAGGCGACA
										GG
chr	499318	T	G	GFY	p.L456	0.006	0.001	1.97	3.86	CCAGAGATG	SEQ
19	84				V	37	66	E-	[2.44-	ACCACGCCC	ID
								07	6.11]	CTTTGCACC	No:
										CACAGTTCT	519
										GCAT[T/G]TG
										GACGCCCCG
										AAAGACCCC
										TACGACCTC
										TACTTTTATG
										C
chr	515180	T	C	KLK10	p.N27	0.013	0.000	4.10	525.	CATAACATC	SEQ
19	60				6S	97	03	E-	15[1	TGGATCAGC	ID
								79	64.3	TGGAGCGTA	No:
									9-	GCATCTGGA	520
									1677	TCAG[T/C]TG
									.55]	GAGCGTATG
										ACTTTATTG
										ATCCAGGAC
										ATGTATTTG
										CA
chr	516283	G	T	SIGLE	p.G54	0.009	0.000	5.23	Inf	TGCTCCTTCT	SEQ
19	92			C9	V	31	00	E-		CCTACCCCT	ID
								56		CGCATGGCT	No:
										GGATTTACC	521
										CTG[G/T]CCC
										AGTAGTTCA
										TGGCTACTG
										GTTCCGGGA
										AGGGGCCAA
										T
chr	519197	C	A	LOC10	p.C38	0.005	0.002	3.44	1.98	GTGTGGACC	SEQ
19	82			012908	X	88	98	E-	[1.3-	AGACGCCAT	ID
				3				03	3.02]	TCCCATCCC	No:
										CCTCCCAGG	522
										GCTG[C/A]GG
										CGGCATCCT
										GGGACCCCA
										CAGCTTCCT
										CTCCCTGGA
										TG
chr	519197	G	C	LOC10	p.G39	0.005	0.002	3.33	1.99	GTGGACCAG	SEQ
19	84			012908	A	88	97	E-	[1.3-	ACGCCATTC	ID
				3				03	3.04]	CCATCCCCC	No:
										TCCCAGGGC	523
										TGCG[G/C]CG
										GCATCCTGG
										GACCCCACA
										GCTTCCTCTC
										CCTGGATGC
										T
chr	519198	G	A	LOC10	p.A58	0.008	0.005	3.85	1.72	CCACAGCTT	SEQ
19	40			012908	T	82	15	E-	[1.23-	CCTCTCCCTG	ID
				3				03	2.42]	GATGCTCCT	No:
										GAGCTGGGA	524
										GCC[G/A]CTC
										ACTGTCCCA
										CTGGGCTCC
										TCCACCTCC
										CCACCCACC
										G
chr	528880	T	A	ZNF88	p.H39	0.018	0.000	1.62	106.	GCAAGGTCT	SEQ
19	30			0	9Q	63	18	E-	63[5	TCAGGCACA	ID
								81	7.96-	AGTTTTGTCT	No:
									196.	AACCAATCA	525
									18]	TCA[T/A]AGA
										ATGCACACG
										GGAGAGCAA
										CCTTACAAA
										TGTAATGAA
										T
chr	528880	A	G	ZNF88	p.M40	0.018	0.000	5.01	102.	GGTCTTCAG	SEQ
19	34			0	1V	87	19	E-	4[55.	GCACAAGTT	ID
								81	69-	TTGTCTAAC	No:
									188.	CAATCATCA	526
									29]	TAGA[A/G]TG
										CACACGGGA
										GAGCAACCT
										TACAAATGT
										AATGAATGT
										GG
chr	528880	G	T	ZNF88	p.M40	0.019	0.000	1.04	99.0	TCTTCAGGC	SEQ
19	36			0	1I	85	20	E-	5[55.	ACAAGTTTT	ID
								84	1-	GTCTAACCA	No:
									178.	ATCATCATA	527
									05]	GAAT[G/T]CA
										CACGGGAGA
										GCAACCTTA
										CAAATGTAA
										TGAATGTGG
										CA
chr	531165	C	T	ZNF83	p.G43	0.007	0.004	2.91	1.65	CCGATGATG	SEQ
19	14				5E	482	537	E-	[1.04-	TGCTAGGGA	ID
								02	2.52]	TGAGTTTAG	No:
										ACCGAAGAC	528
										CTTC[C/T]CA
										CATTCATTA
										CATTTATAA
										GCTTTTTCTC
										CAGTATGAA
										T
chr	532689	G	A	ZNF60	p.P693	0.012	0.000	4.13	1466	CTGCTTGCT	SEQ
19	31			0	L	99	01	E-	.88]2	AAAGGCTTT	ID
								76	02.8	GCCACACTC	NO:
									1-	ATTACACTT	529
									1060	GTAA[G/A]GT
									9.54]	TTCTCTCCAG
										TGTGAAGTC
										CAGTATGTT
										GTTTCAGGT
										G
chr	536445	C	T	ZNF34	p.K51	0.007	0.000	3.82	264.	TTTGAGTGA	SEQ
19	48			7	2K	35	03	E-	49[8	AGACCTTGC	ID
								40	0.69-	CACATTCAT	No:
									866.	TACATTTGT	530
									98]	AAGG[C/T]TT
										TTCTCCAGT
										ATGGATGAC
										CTGATGGGT
										AGTTAGGTT
										TG
chr	537931	C	T	BIRC8	p.A15	0.000	0.000	3.71	Inf	GAAGTCTGA	SEQ
19	62				6T	25	00	E-	[NaN-	TTCAATTCAT	ID
								02	Inf]	TTTCTGTAGT	NO:
										GTCTTTCTGA	531
										G[C/T]GCTCA
										CTAGATCTG
										CAACAAGAA
										CCTCAAGCG
										TTTTATAG
chr	552392	C	T	KIR3D	p.H17	0.009	0.000	1.52	829.	GGATCACTG	SEQ
19	37			L3	2H	80	01	E-	79[1	AGGACCCCT	ID
								52	14.0	TGCGCCTCG	NO:
									5-	TTGGACAGC	532
									6037	TCCA[C/T]GA
									.46]	TGCGGGTTC
										CCAGGTCAA
										CTATTCCAT
										GGGTCCCAT
										GA
chr	552509	C	A	KIR2D	p.P21T	0.010	0.000	8.87	Inf	ATCTTTCTTT	SEQ
19	79			L3		29	00	E-		CCAGGGTTC	ID
								55		TTCTTGCTGC	NO:
										AGGGGGCCT	533
										GG[C/A]CACA
										TGAGGGTGA
										GTCCTTCTCC
										AAACCTTCG
										GGTGTCAT
chr	552848	G	A	KIR2D	p.G36	0.005	0.002	7.72	2.26	CTAGGAGTC	SEQ
19	21			L1	D	64	50	E-	[1.47-	CACAGAAAA	ID
								04	3.49]	CCTTCCCTCC	NO:
										TGGCCCACC	534
										CAG[G/A]TCG
										CCTGGTGAA
										ATCAGAAGA
										GACAGTCAT
										CCTGCAGTG
										T
chr	552867	G	T	KIR2D	p.G17	0.007	0.002	4.86	3.64	TCCAGGGAA	SEQ
19	67			L1	4V	84	17	E-	[2.5-	GGGGAGGCC	ID
								09	5.28]	CATGAACGT	NO:
										AGGCTCCCT	535
										GCAG[G/T]GC
										CCAAGGTCA
										ACGGAACAT
										TCCAGGCTG
										ACTTTCCTCT
										G
chr	552951	A	G	KIR2D	p.T301	0.006	0.003	1.28	2.04	CTCTCCAGG	SEQ
19	21			L1	T	62	25	E-	[1.37-	ACTCTGATG	ID
								03	3.04]	AACAAGACC	NO:
										CTCAGGAGG	536
										TGAC[A/G]TA
										CACACAGTT
										GAATCACTG
										CGTTTTCAC
										ACAGAGAAA
										AA
chr	553300	G	A	KIR3D	p.V11	0.026	0.000	5.79	69.9	CCCACACTC	SEQ
19	36			L1	3M	23	38	E-	5[48.	CCCCACTGG	ID
								118	58-	GTGGTCGGC	NO:
									100.	ACCCAGCAA	537
									73]	CCCC[G/A]TG
										GTGATCATG
										GTCACAGGT
										CAGAGGCTT
										TCCGTCTGG
										GC
chr	553330	C	T	KIR3D	p.P220	0.028	0.000	9.70	1523	AGAACCTCC	SEQ
19	23			L1	L	68	02	E-	.42[3	CTGAGGAAA	ID
								164	76.4-	CTGCCTCTTC	NO:
									6165	TCCTTCCAG	538
									.8]	GTC[C/T]ATA
										TGAGAAACC
										TTCTCTCTCA
										GCCCAGCCG
										GGCCCCAAG
chr	554941	T	G	NLRP2	p.I330	0.007	0.001	8.85	4.3[2	AGGGCCCTG	SEQ
19	21				S	85	80	E-	.1-	AGGGACCTC	ID
								04	8.8]	CGGATCCTG	NO:
										GCGGAGGAG	539
										CCGA[T/G]CT
										ACATAAGGG
										TGGAGGGCT
										TCCTGGAGG
										AGGACAGGA
										GG
chr	560296	A	C	SSC5D	p.T132	0.016	0.000	1.11	Inf	CCACCACTA	SEQ
19	21				6T	67	00	E-		CTCCTGATC	ID
								80		CCACCACGA	NO:
										CCCCTCACC	540
										CCAC[A/C]AC
										TCCTGACCC
										TTCCTCAAC
										CCCTGTCAT
										CACTACTGT
										GT
chr	564163	G	A	NLRP1	p.A86	0.006	0.003	4.86	1.79	CTCCAGTCT	SEQ
19	47			3	0V	86	84	E-	[1.22-	CTCTAAGGC	ID
								03	2.63]	ACACTTGGG	NO:
										GTGAGTCAG	541
										GGCC[G/A]CA
										CACAATAGC
										TTTATGCCAT
										CATCTTGGA
										GCCGATTAA
										A
chr	579108	T	G	ZNF54	p.F402	0.007	0.000	8.20	Inf	TGGAGAAAG	SEQ
19	59			8	V	60	00	E-		GCCTTATAA	ID
								46		ATGCAGTGA	No:
										ATGTGGGAA	542
										ATCA[T/G]TT
										AGGTACCAC
										TGCAGGCTC
										ATTAGACAC
										CAGAGAGTC
										CA
chr	581183	T	C	ZNF53	p.S499	0.005	0.000	3.59	Inf	CTGGAGAAA	SEQ
19	90			0	S	64	00	E-		GGCCTTATG	ID
								34		AGTGCAGTG	No:
										TATGTGGGA	543
										AATC[T/C]TT
										TATCCGAAA
										AACCCACCT
										CATTCGACA
										CCAGACTGT
										TC
chr	583862	T	C	ZNF81	p.A15	0.017	0.009	3.97	1.86	AGACAGATG	SEQ
19	84			4	8A	16	32	E-	[1.45-	ACTCCCCTG	ID
								06	2.37]	ACACATGCA	NO:
										ACTTACACC	544
										TCTT[T/C]GC
										AAACAACGC
										CTCCTCAAC
										ACTCCCTCT
										GTAGGGTTT
										CT
chr	584385	C	T	ZNF41	p.G34	0.007	0.000	6.65	Inf	GTTGATGTT	SEQ
19	05			8	8G	11	00	E-		GAATGAGAT	ID
								43		TGCCCTTCTG	NO:
										AGTAAAACA	545
										TTT[C/T]CCA
										CATTCTTCAC
										ACTCATAAG
										GTCTTTCTCC
										AGTGTGAA
chr	587723	C	A	ZNF54	p.P117	0.005	0.002	1.59	1.93	ATCCCACCA	SEQ
19	21			4	T	53	866	E-	[1.11-	CGTGGAAGT	ID
								02	3.15]	GTACAGGAG	No:
										TGGACCGGA	546
										GGAG[C/A]C
										ACCCTCTTTG
										GTATTAGGA
										AAAGTGCAA
										GATCAGAGC
										AA
chr	141821	G	A	TPO	p.T10	0.009	0.005	3.81	1.69	TTAATTTTAG	SEQ
2	0				T	31	53	E-	[1.22-	AATGAGAGC	ID
								03	2.35]	GCTCGCTGT	No:
										GCTGTCTGT	547
										CAC[G/A]CTG
										GTTATGGCC
										TGCACAGAA
										GCCTTCTTCC
										CCTTCATCT
chr	100450	A	T	TAF1B	p.K27	0.005	0.000	2.18	201.	TCTTTTATTT	SEQ
2	15				9X	39	03	E-	64[6	CAGTCTTGG	ID
								29	0.33-	CCTGACTAC	No:
									673.	GAGGACATC	548
									95]	TAC[A/T]AAA
										AAACAGTAG
										AAGTTGGAA
										CATTTTTAG
										ATTTGCCTC
										G
chr	117744	C	T	GREB	p.S171	0.001	0.000	3.24	11.7	TCCAGCAAG	SEQ
2	03			1	3F	47	13	E-	5[3.3	ACCCGGGCC	ID
								03	7-	AGCGAGGTG	No:
									40.9	CAAGAGCCC	549
									2]	TTCT[C/T]CC
										GCTGCCACG
										TGCACAACT
										TCATCATCCT
										GAACGTGGA
										C
chr	179980	C	T	MSGN	p.G72	0.005	0.002	8.49	1.84	CTCCCTGTCC	SEQ
2	01			1	G	39	93	E-	[1.2-	AGCTGTGGC	ID
								03	2.84]	TGGGCTGCC	No:
										CTGTGAGCA	550
										CGG[C/T]GGG
										GCCAGCAGT
										GGGGGCAGC
										GAAGGCTGC
										AGTGTCGGT
										G
chr	239295	C	T	KLHL2	p.C865	0.011	0.008	4.80	1.38	TCCTCCCCC	SEQ
2	01			9	C	03	04	E-	[1.01-	ACATGCCCT	ID
								02	1.87]	GCCCTGTGT	No:
										TCAGACACG	551
										GCTG[C/T]GT
										CGTGATAAA
										GAAATATAT
										TCAAAGCGG
										CTGACATCA
										GC
chr	243023	G	A	TP53I3	p.R258	0.003	0.000	2.03	16.4	TTGTCCCTA	SEQ
2	58				X	93	20	E-	[5.5-	GACCTCAGC	ID
								04	49.2]	AAACTGGTG	No:
										ATCAGACTT	552
										CCTC[G/A]CT
										TAAAAAGTA
										GCTTTGAAA
										ACAGGGGCC
										CATTGATGT
										CA
chr	249302	C	T	NCOA	p.A64	0.009	0.006	3.26	1.43	AAACCAGTC	SEQ
2	62			1	1A	56	69	E-	[1.04-	ACAAACTAG	ID
								02	1.98]	TGCAGCTTTT	No:
										GACAACAAC	553
										TGC[C/T]GAA
										CAGCAGTTA
										CGGCATGCT
										GATATAGAC
										ACAAGCTGC
										A
chr	264151	G	A	HADH	p.L661	0.010	0.007	3.77	1.41	TAGCCACTC	SEQ
2	98			A	L	05	13	E-	[1.03-	AAACGGACT	ID
								02	1.94]	TACACTTCA	No:
										GACTTAGGA	554
										GGCA[G/A]CT
										TCAGACTCG
										CTAAAATAC
										TATCCATGT
										CAGAATTCA
										AA
chr	266633	C	T	DRC1	p.T331	0.005	0.003	1.29	1.91	TACAACTTG	SEQ
2	49				I	856	08	E-	[1.11-	CAGGTGCTG	ID
								02	3.07]	AAGAAGAGA	No:
										GATGAAGAA	555
										AGCA[C/T]AG
										TAATTAAAT
										CCCAGCAGA
										AGAGGAAGA
										TCAATCGGT
										AA
chr	268523	C	G	CIB4	p.G42	0.017	0.000	2.59	Inf	ACCTGGTCC	SEQ
2	40				R	40	00	E-		ATGGTGAGC	ID
								95		GTTGCCTCCT	No:
										TGTAGTACT	556
										TCC[C/G]AGG
										AGGGCAGAG
										CTTCAGGAA
										GGTGTCATG
										GATGCTGAA
										A
chr	292460	G	A	FAM1	p.V53	0.005	0.003	4.86	1.55	AGGTCCTCA	SEQ
2	48			79A	6V	64	66	E-	?1.01-	CCGGGAAGC	ID
								02	2.36?	TGCACGACG	No:
										TGTGCTTGG	557
										TGGT[G/A]AC
										TGGGGAGGT
										GAGGCCCCC
										CAGCCTGTG
										TGCTGTGCA
										TT
chr	315951	C	T	XDH	p.R607	0.005	0.003	3.21	1.61	TCACTTGAT	SEQ
2	30				Q	64	51	E-	[1.06-	CTTGGCGTG	ID
								02	2.45]	GGCCCGGGT	No:
										GCTGGTGAC	558
										CAGC[C/T]GG
										AGAGACAGC
										TCATTCTCGT
										AGCGAGGAA
										TGTCGTCAC
										A
chr	322890	C	T	SPAST	p.P34P	0.021	0.000	3.17	2161	CTCCCAGGC	SEQ
2	02					81	01	E-	.13[3	CTCCGCCCC	ID
								123	01.0	CTTGCCTGG	No:
									2-	CCCCCGCCC	559
									1551	CTCC[C/T]GC
									5.36]	CGCCGGGCC
										GGCCCCTCC
										GCCCGAGTC
										GCCGCATAA
										GC
chr	489827	A	T	LHCG	p.L16	0.008	0.000	3.94	29.6	GAGCGCCTC	SEQ
2	64			R	Q	58	29	E-	3[15.	GCGCAGCGC	ID
								28	93-	TCGTGGCAG	No:
									55.1	CGGCGGCTG	560
									2]	CAGC[A/T]GC
										AGCAGCAGC
										TTCAGCAGC
										TGCAGCGCC
										GAGAACCGC
										TG
chr	624498	C	T	B3GN	p.N17	0.008	0.006	3.07	1.47	GAAGGCAAG	SEQ
2	65			T2	0N	82	00	E-	[1.05-	CAATCCGGG	ID
								02	2.06]	AATCCTGGG	No:
										GCCAAGAAA	561
										GCAA[C/T]GC
										AGGGAACCA
										AACGGTGGT
										GCGAGTCTT
										CCTGCTGGG
										CC
chr	743265	C	T	TET3	p.P115	0.019	0.000	5.92	2204	AGGTGCTCA	SEQ
2	94				3P	61	01	E-	.62[3	CCGCCTTCC	ID
								115	06.7-	CCCGCGAGG	No:
									1584	TCCGACGCC	562
									7.05]	TGCC[C/T]GA
										GCCTGCCAA
										GTCCTGCCG
										CCAGCGGCA
										GCTGGAAGC
										CA
chr	744793	G	A	SLC4A	p.S472	0.006	0.003	7.75	1.78	CCCCGATTT	SEQ
2	68			5	S	37	58	E-	[1.2-	CATGCATGG	ID
								03	2.66]	CTGGCATCT	No:
										CTCCATCAT	563
										CCCC[G/A]CT
										GCTTGTTCC
										GCCGGCCCC
										GCCACTGCC
										AGCCCCGCC
										GC
chr	747513	G	C	DQX1	p.T158	0.005	0.003	2.25	1.67	CCTCATCTA	SEQ
2	92				T	88	53	E-	[1.1-	GTACCAGCA	ID
								02	2.52]	CGCCCCAGG	NO:
										CTCCAGTGC	564
										CTCG[G/C]GT
										CGAGGCCAC
										CTCCTGCAG
										AAGCAGCCT
										GTCCCAGCA
										GA
chr	868317	G	C	RNF10	p.L421	0.006	0.003	5.86	1.8[1	CTCTTCTTCT	SEQ
2	51			3	V	62	69	E-	.22-	CAAAGTAAT	ID
								03	2.66]	CAATTAGTA	NO:
										AACCATGAC	565
										CAA[G/C]GTA
										TGTACTGAG
										AAACAGGGC
										TGGGTGTGA
										AGAGTAAAA
										C
chr	959456	G	A	PROM	p.G45	0.005	0.000	8.10	571.	CTATTCGTG	SEQ
2	67			2	0D	64	01	E-	38[7	GTGCTCTGC	ID
								32	7.15-	AACCTGCTG	No:
									4231	GGCCTCAAT	566
									.98]	CTGG[G/A]CA
										TCTGGGGCC
										TGTCTGCCA
										GGGACGACC
										CCAGCCACC
										CA
chr	981282	G	C	ANKR	p.L102	0.007	0.000	4.61	Inf	GTCTTTGCCT	SEQ
2	58			D36B	1L	35	00	E-		GCTCTCTCTT	ID
								27		TGCTTCTCCA	No:
										GTTTGGAAC	567
										G[G/C]AGCGT
										TGTGTTTTCA
										TCTGTCAGA
										GCAGCAAGC
										TGTCCAC
chr	981283	G	A	ANKR	p.T100	0.017	0.000	7.10	240.	ATCTGTCAG	SEQ
2	13			D36B	3M	16	07	E-	02[5	AGCAGCAAG	ID
								60	8.84-	CTGTCCACT	NO:
									979.	ATAACAGGC	568
									16]	TATC[G/A]TT
										TTTGCTAAT
										GTTTCCCCAT
										TCCGTTTTAG
										AGCCTTTTG
chr	996517	G	A	TSGA1	p.S503	0.005	0.001	1.76	3.76	TAATACAGA	SEQ
2	98			0	S	21	39	E-	[2.09-	GTTCCCTAG	ID
								05	6.31]	TAGAAGACA	NO:
										AATCTGCAA	569
										GAGC[G/A]G
										ACACTTTTTC
										AAACTGAAC
										CTTCTGAAG
										CTCCTCTTCC
										A
chr	108486	G	T	RGPD	RGPD4	0.025	0.000	1.47	67.6	ACTTTAACA	SEQ
2	338			4	(NM_	25	38	E-	[34.1	GTGTTTTCTT	ID
					182588:			74	8-	TCTTTTCTTT	NO:
					exon19:				133.	TTTTTTTTTT	570
					c.				72]	A[G/T]TTGCA
					2606-					ACTACTGGC
					1G > T)					CCTTCAGTA
										TATTATAGT
										CAGTCACC
chr	109347	T	G	RANB	p.L96	0.014	0.000	1.94	Inf	ATTAGCGTT	SEQ
2	813			P2	L	95	00	E-		CAGTGGAAT	ID
								89		TAAACCCAA	No:
										CACAAAAAG	571
										ATCT[T/G]GT
										GTTGAAGAT
										TGCAGAATT
										GCTTTGTAA
										AAATGATGT
										TA
chr	112922	C	G	FBLN7	p.P87	0.007	0.004	7.23	1.73	TCCATCTCTC	SEQ
2	601				A	35	26	E-	[1.19-	CTTACAGTTT	ID
								03	2.51]	CCTGCCCGG	NO:
										CTCTGAACA	572
										CC[C/G]CCGC
										AGACGGCAG
										AAAGTTTGG
										AAGCAAGTA
										CTTAGTGGA
chr	113940	G	A	PSD4	p.A52	0.022	0.000	6.94	2577	CCATGAGGA	SEQ
2	187				T	55	01	E-	.18[3	TCCACCGGA	ID
								133	59.1-	GCCTTTCGA	NO:
									1849	GGAGCAAAC	573
									5.63]	CTGG[G/A]CC
										ACTGACCCT
										CCTGAACCT
										ACCAGACAA
										AATGTTCCT
										CC
chr	114500	C	T	SLC35	p.E224	0.009	0.006	4.53	1.43	GCAGTAAGT	SEQ
2	349			F5	K	07	35	E-	[1.03-	TTCCCCACA	ID
								02	1.99]	GTTTTCAGT	NO:
										ATGGATTCT	574
										TGTT[C/T]TT
										TCACAGGAT
										ATGACATGC
										GAGACAACT
										TTGCTTCCA
										AT
chr	132238	T	C	TUBA3	p.A27	0.007	0.004	2.79	1.55	TCCACTTCCC	SEQ
2	100			D	8A	35	75	E-	[1.07-	CCTGGCCAC	ID
								02	2.25]	CTATGCCCC	NO:
										AGTCATCTC	575
										AGC[T/C]GAG
										AAGGCCTAC
										CACGAGCAG
										CTGTCTGTG
										GCCGAGATC
										A
chr	136418	A	G	R3HD	p.H59	0.005	0.002	1.00	2.18	TTATGATCCT	SEQ
2	868			M1	6R	64	60	E-	[1.42-	AGATGCCAG	ID
								03	3.33]	CCTGTTATTG	No:
										CGCTCCAGG	576
										CC[A/G]CTAT
										CACTCCAGC
										CAACCTCAG
										TATCGCCCA
										GTCCCTTCT
chr	141232	C	T	LRP1B	p.A31	0.007	0.011	2.07	0.67	GCCCAGTAG	SEQ
2	800				78T	84	71	E-	[0.47-	AGTCTACGA	ID
								02	0.95]	TTAACATAA	No:
										TCTATTGTTA	577
										GTG[C/T]CAT
										AGGTCTAGA
										AATCTTGGT
										TTCTATGAC
										AACACTCTG
										A
chr	152982	T	C	STAM2	p.M39	0.006	0.003	9.98	1.73	ATAATTTAG	SEQ
2	745				2V	62	83	E-	[1.17-	AAAATGTTC	ID
								03	2.56]	TCAAAAAAC	No:
										ATGCTCACC	578
										TGCA[T/C]TG
										GAACCCCAG
										ATGATGCAG
										GTGGGTAAT
										GTGCTGGAG
										GG
chr	165984	C	T	SCN3A	p.V10	0.012	0.007	7.31	1.71	GGGTTGTTT	SEQ
2	284				841	25	22	E-	[1.28-	ATGAATGAC	ID
								04	2.27]	ATATAATCA	No:
										TTTTCATCGA	579
										TTA[C/T]GTA
										TTTTTCAACA
										CTGCTTCCA
										GTACCTACA
										CCACTGGTG
chr	171070	G	A	MYO3	p.G13	0.005	0.003	4.93	1.68	CCAGCGGTT	SEQ
2	982			B	9R	205	108	E-	[0.95-	GGATGAAGC	ID
								02	2.77]	AATGATCTC	No:
										ATACATCTT	580
										GTAC[G/A]GG
										GCCCTCTTG
										GTAAGAACA
										TCTATCAAA
										TGGGGTATG
										AC
chr	178096	G	A	NFE2L	p.L286	0.005	0.003	6.39	1.86	AGATCAGAA	SEQ
2	406			2	F	64	04	E-	[1.22-	ACATCAATG	ID
								03	2.84]	GGCCCATTT	No:
										AGAAGTTCA	581
										GAGA[G/A]T
										GAATGGCTT
										AAAGTAGCA
										GGTGAGGGC
										ATGCTGTTG
										CTG
chr	186661	A	G	FSIP2	p.R333	0.006	0.003	1.12	1.72	ATCGTGTTCT	SEQ
2	602				6G	86	99	E-	[1.16-	ACTAGAAAC	ID
								02	2.56]	AAAGTACAA	NO:
										GACCACAGA	582
										CCA[A/G]GG
										GAATCTAAC
										TTTGGTAGTT
										TTGATCAGA
										CCATGAAAG
										G
chr	186678	A	T	FSIP2	p.K68	0.025	0.000	3.65	Inf	TTTCTCCTAA	SEQ
2	577				00N	49	00	E-		GTCAACACT	ID
								151		AAGCACGAG	NO:
										CAGCCTGAA	583
										AAA[A/T]TTT
										TTGTCACTA
										AGTAAATGT
										TGTCAGACC
										ACAGCCAGT
										G
chr	187605	G	A	FAM1	p.R95	0.007	0.004	2.40	1.58	GTATTTATGT	SEQ
2	000			71B	H	11	51	E-	[1.09-	TGAAAGTCC	ID
								02	2.3]	AGGTGAATG	NO:
										ACATCATCA	584
										GTC[G/A]TCA
										GTACCTGAG
										CCAAGCAGT
										TGTAGAAGT
										GTTTGTAAA
										C
chr	209302	G	A	PTH2R	p.S82S	0.006	0.000	1.50	743.	GACTCATTT	SEQ
2	329					62	01	E-	52[1	GTTGGCCCA	ID
								38	01.0	GAGGAACAG	No:
									1-	TGGGGAAAA	585
									5472	TATC[G/A]GC
									.96]	TGTTCCATG
										CCCTCCTTAT
										ATTTATGAC
										TTCAACCAT
										A
chr	211068	C	A	ACAD	p.R311	0.007	4.63	0.002	3.5[2	AACTGTTTT	SEQ
2	107			L	M	11	04	E-	.37-	GCCAAAAGC	ID
								08	5.16]	TTTTCTTTGT	NO:
										TTAACATAG	586
										TTC[C/A]TGG
										TTTCTTCAAA
										CATGAATTC
										ACTAGCTGA
										AATTGCCAC
chr	216285	C	T	FN1	p.V52	0.001	not	4.03	Inf	ATGTGCCCC	SEQ
2	492				7M	47	found	E-		TCTTCATGA	ID
								06		CGCTTGTGG	NO:
										AATGTGTCG	587
										TTCA[C/T]AT
										TGTAAGTGA
										TGTCATCAA
										CAATGCACT
										GATCTGTTT
										AG
chr	233246	A	G	ALPP	p.E451	0.006	0.004	8.56	1.71	AGCCCCGAG	SEQ
2	249				G	86	01	E-	[1.17-	TATCGGCAG	ID
								03	2.52]	CAGTCAGCA	NO:
										GTGCCCCTG	588
										GACG[A/G]A
										GAGACCCAC
										GCAGGCGAG
										GACGTGGCG
										GTGTTCGCG
										CGC
chr	233498	C	G	EFHD	p.P34	0.010	0.000	2.59	Inf	GAGAGTGGC	SEQ
2	515			1	R	05	00	E-		CCCCAGCTG	ID
								36		GCTCCCCTC	NO:
										GGCGCCCCA	589
										GCCC[C/G]GG
										AGCCCAAGC
										CCGAGCCCG
										AGCCTCCCG
										CCCGTGCGC
										CC
chr	234229	C	T	SAG	p.T125	0.005	0.003	1.25	1.78	CTTAAAAAG	SEQ
2	468				M	88	32	E-	[1.17-	CTGGGGAGC	ID
								02	2.7]	AACACGTAC	NO:
										CCCTTTCTCC	590
										TGA[C/T]GGT
										GGGTGACTC
										CTCCGGCCA
										GCCCTGCTT
										CCTTCACCC
										G
chr	237029	C	T	AGAP	p.C711	0.025	0.000	9.57	943.	TGCTGGCAC	SEQ
2	013			1	C	25	03	E-	45[2	ACGGCTCCC	ID
								145	99.2	GGGACGAGG	NO:
									2-	TGAACGAGA	591
									2974	CCTG[C/T]GG
									.8]	GGAGGGAGA
										CGGCCGCAC
										GGCGCTGCA
										TCTGGCCTG
										CC
chr	238973	A	G	SCLY	p.K60	0.002	0.000	5.74	4.37	AACGACTCC	SEQ
2	062				E	94	67	E-	[2.37-	CCTGGAGCC	ID
								05	8.05]	AGAAGTTAT	NO:
										CCAGGCCAT	592
										GACC[A/G]A
										GGCCATGTG
										GGAAGCCTG
										GGGAAATCC
										CAGCAGCCC
										GTA
chr	240982	G	A	PRR21	p.R53	0.021	0.000	1.26	480.	GGGTGAAGA	SEQ
2	243				W	32	05	E-	79[1	GCCGTGGAT	ID
								112	76.3	GAAGGGCCG	NO:
									8-	TGGGTGAAG	593
									1310	AGCC[G/A]TG
									.53]	GATGAAGGG
										CCATGGGTG
										AAGAGCCGT
										GGATGAAGG
										GC
chr	242154	G	A	ANO7	NM_	0.005	0.000	3.42	7.1[3	GCAAGCAGG	SEQ
2	318				001001891:	89	80	E-	-	TCATCAACA	ID
					exon18:			04	16.5]	ACATGCAGG	NO:
					c					AGGTCCTCA	594
					.1988 +					TCCC[G/A]TG
					1G > A					AGTCCCCCA
										CTCCTCCCTG
										GGTGGCATC
										CAAGGACCG
										A
chr	242207	T	A	HDLB	p.T14S	0.009	0.006	4.29	1.43	ACCACACAC	SEQ
2	024				P	07	34	E-	[1.02-	CTCTTAATG	ID
								02	2.02]	CTTACAAAA	NO:
										TGCATCATG	595
										ACAG[T/A]TG
										CTACAAAAA
										GCCAGCGGT
										CTCTCTCTGC
										AAGGTGCAT
										C
chr	242312	C	T	FARP2	p.H45	0.008	0.006	4.12	1.45	TGGGCAGAC	SEQ
2	655				Y	82	12	E-	[1.03-	TCTCTTGCCC	ID
								02	2.03]	AGAATGCAA	NO:
										GAGAAGCAC	596
										CTG[C/T]ACC
										TCAGAGTAA
										AGCTGCTGG
										ACAACACCA
										TGGAAATAT
										T
chr	314753	G	A	LZTS3	p.L93	0.009	0.006	1.14	1.55	CACTGCCCC	SEQ
20	1				L	56	19	E-	[1.12-	GCAGCTCAC	ID
								02	2.14]	CATTGAGGT	NO:
										AGAGGGAGT	597
										TGGC[G/A]AG
										ACCCTTGTC
										CTCTGAGGG
										GTAGCGGCC
										CGGCCTCTC
										CC
chr	468011	T	C	PRNP	p.S55P	0.005	0.000	1.14	314.	GTGGCTGGG	SEQ
20	8					64	02	E-	81[7	GGCAGCCCC	ID
								31	4.2-	ATGGTGGTG	NO:
									1335	GCTGGGGAC	598
									.71]	AGCC[T/C]CA
										TGGTGGTGG
										CTGGGGTCA
										AGGAGGTGG
										CACCCACAG
										TC
chr	317569	C	T	BPIFA	p.G12	0.005	0.002	9.96	1.86	AAAAGATGC	SEQ
20	87			2	G	15	77	E-	[1.2-	TTCAGCTTTG	ID
								03	2.9]	GAAACTTGT	NO:
										TCTCCTGTGC	599
										GG[C/T]GTGC
										TCACTGGGA
										CCTCAGAGT
										CTCTTCTTGA
										CAATCTTG
chr	340785	G	A	CEP25	p.E881	0.010	0.007	4.80	1.37	CTGGCACCA	SEQ
20	17			0	K	78	88	E-	[1.01-	GCAGGAGCT	ID
								02	1.86]	GGCAAAGGC	No:
										TCTGGAGAG	600
										CTTA[G/A]AA
										AGGGAAAAA
										ATGGAGCTG
										GAAATGAGG
										CTAAAGGAG
										CA
chr	341303	T	C	ERGIC	p.F76F	0.007	0.000	3.01	79.9	CGCGGGGAG	SEQ
20	30			3		11	09	E-	3[38.	ATAAACTGA	ID
								34	93-	AGATCAACA	No:
									164.	TCGATGTAC	601
									12]	TTTT[T/C]CC
										GCACATGCC
										TTGTGCCTGT
										GAGTACCTC
										ACCATGGGT
										G
chr	462798	G	A	NCOA	p.Q12	0.011	0.000	5.51	Inf	GGGTGGCTA	SEQ
20	39			3	55Q	27	00	E-		TGATGATGC	ID
								65		AGCAGCAGC	No:
										AGCAGCAGC	602
										AACA[G/A]C
										AGCAGCAGC
										AGCAGCAGC
										AGCAGCAAC
										AGCAACAGC
										AAC
chr	485033	G	A	SLC9A	p.S519	0.009	0.006	3.58	1.44	GGCCGCCTT	SEQ
20	06			8	S	07	33	E-	[1.03-	TCCTCCCTGC	ID
								02	2]	TCAGGGCAA	No:
										CACTGTGGA	603
										GTC[G/A]GAG
										CACCTGTCG
										GAGCTCACG
										GAGGAGGAG
										TACGAGGCC
										C
chr	491978	G	A	PTPN1	p.G30	0.005	0.002	6.45	2.14	CACTGAAGT	SEQ
20	54				8S	541	6	E-	[1.23-	TAGAAGTCG	ID
								03	3.49]	GGTCGTGGG	No:
										GGGAAGTCT	604
										TCGA[G/A]GT
										GCCCAGGCT
										GCCTCCCCA
										GCCAAAGGG
										GAGCCGTCA
										CT
chr	609019	C	T	LAMA	p.V17	0.011	0.007	2.52	1.43	ACCCTGCCA	SEQ
20	32			5	35M	27	93	E-	[1.06-	CATCATCTC	ID
								02	1.92]	AGCTCCCTC	No:
										ACCTGCAGC	605
										ACCA[C/T]AT
										CCGGCCTGC
										TCTCCATGG
										GGACAAAGA
										CATCTCCCC
										GC
chr	612963	C	A	SLCO4	p.G40	0.011	0.008	4.76	1.35	TCTGCCTGG	SEQ
20	67			A1	1G	52	55	E-	[1.01-	CCGGGGCCA	ID
								02	1.81]	CCGAGGCCA	No:
										CTCTCATCA	606
										CCGG[C/A]AT
										GTCCACGTT
										CAGCCCCAA
										GTTCTTGGA
										GTCCCAGTT
										CA
chr	622005	C	T	HELZ2	p.S334	0.005	0.003	3.47	1.63	GGTGCATCC	SEQ
20	87				S	15	16	E-	[1.05-	TCTGCCGAT	ID
								02	2.54]	AGTTGGTTG	No:
										GTGAGATGG	607
										GGCC[C/T]GA
										GGCCACGCT
										GCTGCGGTT
										GAACTCCAG
										GGCCAGGGC
										AG
chr	109429	T	G	TPTE	p.Q17	0.005	0.000	9.09	14.4	ACTTACCCG	SEQ
21	55				3P	88	41	E-	3[8.7	CCTTCTTATC	ID
								18	8-	AGCTTTTCA	No:
									23.7]	AGTTGTCTTT	608
										TT[T/G]GATG
										AAACAGATG
										AAAAATTCT
										TAACAGAAT
										AATAAGTCG
chr	109429	C	A	TPTE	p.L164	0.012	0.000	1.16	16.3	CAAGTTGTC	SEQ
21	81				L	75	79	E-	9[11.	TTTTTTGATG	ID
								38	59-	AAACAGATG	No:
									23.1	AAAAATTCT	609
									7]	TAA[C/A]AGA
										ATAATAAGT
										CGTAGAAGT
										CGAAGTAAA
										TGTGTCCAT
										C
chr	149827	A	G	POTE	p.R58	0.022	0.000	8.43	216.	CACTTCTGG	SEQ
21	21			D	G	79	11	E-	23[5	AGACCACGA	ID
								67	3.26-	CGACTCCTTT	No:
									877.	ATGAAGATG	610
									86]	CTC[A/G]GGA
										GCAAGATGG
										GCAAGTGTT
										GCCGCCACT
										GCTTCCCCT
										G
chr	349274	C	G	SON	p.R196	0.008	0.000	2.93	Inf	GCATTTCCC	SEQ
21	26				3R	33	00	E-		CAAGCCGCC	ID
								36		GCAGCCGCA	No:
										CCCCCAGCC	611
										GCCG[C/G]AG
										CCGCACCCC
										CAGCCGCCG
										CAGCCGCAC
										CCCCAGCCG
										CC
chr	427708	G	A	ALV2	p.G40	0.010	0.006	1.46	1.51	GGAGAGCCA	SEQ
21	96				8R	05	66	E-	[1.1-	CCAGAAGGC	ID
								02	2.08]	GACCGAGGA	NO:
										GCTGCGGCG	612
										TTGC[G/A]GG
										GCTGACATC
										CCCAGCCAG
										GAGGCCGAC
										AAGATGTTC
										TT
chr	434126	G	C	ZBTB2	p.A52	0.007	0.005	3.45	1.49	ACCAAATTC	SEQ
21	40			1	2G	60	10	E-	[1.04-	GTCTTTATTC	ID
								02	2.15]	AAATCAGAA	NO:
										TCTGGAAAA	613
										TCT[G/C]CAT
										CAAGGAGAG
										TAGGGCTTG
										AGCCTTCCT
										CAAAATTAT
										C
chr	456707	G	A	DNMT	p.S276	0.024	0.000	1.25	2810	GCACCAGAT	SEQ
21	74			3L	S	75	01	E-	.21[3	TGTCCACGA	ID
								145	91.9	ACATCCAGA	No:
									4-	AGAAGGGCC	614
									2014	TGGG[G/A]CT
									9]	GCCTGGCTT
										GGGCCGTGC
										GTACTGCAG
										GAGCCGGTG
										GA
chr	457866	G	A	TRPM	p.V15	0.008	0.005	3.32	1.49	CCCGCAGTA	SEQ
21	70			2	3M	33	61	E-	[1.05-	CGTCCGAGT	ID
								02	2.11]	CTCCCAGGA	NO:
										CACGCCCTC	615
										CAGC[G/A]TG
										ATCTACCAC
										CTCATGACC
										CAGCACTGG
										GGGCTGGAC
										GT
chr	459947	T	C	KRTA	p.P378	0.011	0.000	1.15	1313	GCCGCCCCG	SEQ
21	69			P10-4	P	76	01	E-	.63[1	TGTGCAGGC	ID
								68	81.2	CCGCCTGCT	NO:
									8-	GCGTGCCCG	616
									9519	TCCC[T/C]TC
									.28]	CTGCTGTGC
										TCCCACCTC
										CTCCTGCCA
										ACCCAGCTG
										CT
chr	459998	T	A	KRTA	p.T197	0.008	0.000	4.27	Inf	CAGCAAGCC	SEQ
21	67			P10-5	S	82	00	E-		GGCTGACAG	ID
								53		CTAGACTGC	NO:
										TGGCAGCAT	617
										GAAG[T/A]G
										GAAGCCCCA
										GAGCAGACG
										GGCACACAG
										CAGATGGGT
										TTG
chr	460000	G	A	KRTA	p.P138	0.026	0.000	3.02	Inf	ATGAAGAGG	SEQ
21	42			P10-5	P	47	00	E-		AATCCTCAG	ID
								158		AACAGGTGG	NO:
										GCACACAGC	618
										ACAC[G/A]G
										GCTTGCAGC
										AGACAGGCA
										CACAGCAGG
										ACTGCTGGC
										AGG
chr	460206	C	T	KRTA	p.C42	0.012	0.001	7.61	10.2	CCGACTCCT	SEQ
21	47			P10-7	C	75	26	E-	4[7.4	GGCAGGTGG	ID
								31	3-	ACGACTGCC	NO:
									14.1	CAGAGAGCT	619
									2]	GCTG[C/T]GA
										GCCCCCCTG
										CTGCGCCCC
										CAGCTGCTG
										CGCCCCGGC
										CC
chr	460324	T	C	KRTA	p.S153	0.014	0.000	3.77	Inf	TGGAGCTTC	SEQ
21	74			P10-8	P	22	00	E-		CTCCCCATG	ID
								85		CTGCCAGCA	NO:
										GTCTAGCTG	620
										CCAG[T/C]CA
										GCTTGCTGC
										ACCTTCTCCC
										CATGCCAAC
										AGGCCTGCT
										G
chr	461174	T	C	KRTA	p.S98P	0.017	0.000	3.00	1974	CTGCCAGCA	SEQ
21	08			P10-12		40	01	E-	.74[2	GTCTAGCTG	ID
								102	74.3-	CCAGCCGGC	NO:
									1421	TTGCTGCAC	621
									6.51]	CTCC[T/C]CC
										CCCTGCCAG
										CAGGCCTGC
										TGCGTGCCC
										GTCTGCTGC
										AA
chr	461914	G	A	UBE2	p.P60P	0.008	0.005	3.46	1.47	ACATTTTGG	SEQ
21	00			G2		33	68	E-	[1.04-	ACGCATCCA	ID
								02	2.08]	CGTTAGCTC	NO:
										CACTTTCGTC	622
										ATT[G/A]GGC
										TCTGAAAGA
										AAAGGGAAC
										ACCCTCCAT
										GTAAAAGGG
										A
chr	465964	G	A	ADAR	p.K28	0.008	0.005	2.59	1.5[1	TCGTGGATG	SEQ
21	59			B1	1K	33	59	E-	.06-	GTCAGTTCTT	ID
								02	2.12]	TGAAGGCTC	NO:
										GGGGAGAAA	623
										CAA[G/A]AA
										GCTTGCCAA
										GGCCCGGGC
										TGCGCAGTC
										TGCCCTGGC
										CG
chr	185627	T	C	PEX26	p.Y10	0.005	0.002	2.61	1.82	AATGGATCG	SEQ
22	34				9H	21	87	E-	[1.03-	GTGGCAAGA	ID
								02	3.01]	AGTCCTCTC	NO:
										CTGGGTCCT	624
										TCAG[T/C]AT
										TACCAGGTC
										CCTGAAAAG
										CTACCCCCC
										AAAGTCCTG
										GA
chr	240867	G	A	ZNF70	p.C198	0.013	0.000	4.80	1525	TGAGGGCTG	SEQ
22	34				C	48	01	E-	.31[2	AGCTCTGGC	ID
								79	11.0	GGAAGGCCT	NO:
									3-	TCCCACACT	625
									1102	CCCG[G/A]CA
									4.83]	CTCGTAGGG
										CTTCTCCCCG
										GTGTGGATG
										ATCTGGTGC
										C
chr	250071	G	A	GGT1	p.A42	0.008	0.002	5.51	3.34	AGCCTCCAA	SEQ
22	72				T	82	66	E-	[2.34-	GGAACCTGA	ID
								09	4.76]	CAACCATGT	NO:
										GTACACCAG	626
										GGCT[G/A]CC
										GTGGCCGCG
										GATGCCAAG
										CAGTGCTCG
										AAGATTGGG
										AG
chr	250072	A	G	GGT1	p.K52	0.008	0.002	2.23	3.52	CACCAGGGC	SEQ
22	02				E	82	52	E-	[2.45-	TGCCGTGGC	ID
								09	5.05]	CGCGGATGC	NO:
										CAAGCAGTG	627
										CTCG[A/G]AG
										ATTGGGAGG
										TGAGCAGGG
										CAGGGCATG
										GGACATGGG
										CC
chr	268799	A	G	SRRD	p.R37	0.007	0.000	1.96	Inf	CTCGACGGC	SEQ
22	67				R	11	00	E-		CGCGGCGGA	ID
								08		GGGAGGCGG	NO:
										CGCCCCGGG	628
										GGAG[A/G]G
										AGGCGGCGC
										CCCGGGGGA
										GAGAGGCGG
										CGCCCCGGG
										GCC
chr	299132	C	T	THOC	p.V52	0.010	0.007	4.97	1.38	ACTCCTTCA	SEQ
22	78			5	3M	05	28	E-	[1.01-	CCTACCATG	ID
								02	1.9]	TAATCCTCA	NO:
										TGGGCAACT	629
										GTCA[C/T]CC
										ATTTCACCA
										GGCGAGAGA
										CAACCTTGG
										CAGGGAAGA
										GG
chr	325904	C	T	RFPL2	p.R50	0.005	0.003	3.92	1.56	GGGCCTTTT	SEQ
22	48				H	88	78	E-	[1.03-	ATTGGTGAG	ID
								02	2.35]	ATTCCCACC	No:
										TCCCACTGG	630
										GTCA[C/T]GC
										CCTTCCACA
										CCCTCTAAC
										CTGATGAGG
										CTTTGATTTA
										A
chr	325904	G	A	RFPL2	p.I42I	0.005	0.003	3.59	1.96	CACCTCCCA	SEQ
22	71					88	01	E-	[1.29-	CTGGGTCAC	ID
								03	2.97]	GCCCTTCCA	No:
										CACCCTCTA	631
										ACCT[G/A]AT
										GAGGCTTTG
										ATTTAATTAT
										AACAGGGAA
										TTAGGTTTTT
chr	381203	C	G	TRIOB	p.T599	0.008	0.000	4.23	966.	AGAGCCTCC	SEQ
22	59			P	R	58	01	E-	49[1	TCTCCCAAT	ID
								50	32.3	AGAGCTACA	No:
									8-	CGAGACAAC	632
									7056	CCCA[C/G]AA
									.38]	CATCCTGTG
										CCCAGCGGG
										ACAATCCCA
										GAGCCTCCA
										GA
chr	381208	C	T	TRIOB	p.P754	0.021	0.000	3.86	2405	CGAGACAAC	SEQ
22	24			P	L	08	01	E-	.39[3	CCCAGAACA	ID
								124	34.9	TCCTGTGCC	No:
									2-	CAGCGGGAC	633
									1727	AATC[C/T]CA
									5.56]	GAGCCTCCT
										CTCCTAACA
										GAACCATCC
										AACAAGAGA
										AC
chr	381224	G	T	TRIOB	p.G12	0.026	0.000	4.02	Inf	GGCCCAGAG	SEQ
22	49			P	96W	23	00	E-		ACAGCCAGG	ID
								141		GCCCCAGGC	No:
										GCAGTGCAG	634
										CAGC[G/T]GG
										GGCCGCACC
										CACAGCCCT
										GGCCGTGCA
										GAGGTGGAG
										CG
chr	425646	G	A	TCF20	p.S195	0.015	0.000	1.36	Inf	ACTGCCCCC	SEQ
22	89				1S	44	00	E-		CTCACCCCC	ID
								91		GCTCCGACT	No:
										GCTCTGTGC	635
										TGAG[G/A]CT
										GCCTTTCGC
										GGTCTTGTTC
										TGCAAGGGG
										GGGAGAGGG
										C
chr	466578	T	C	PKDR	p.R447	0.006	0.002	2.21	2.21	ATGTGTGCT	SEQ
22	81			EJ	G	51	96	E-	[1.33-	ATGGCTTTT	ID
								03	3.47]	GGTCCTTGG	No:
										AGCACGTGG	636
										ACCC[T/C]CT
										TATCAGAAA
										ACGCTGTCC
										TAGAGTCCT
										TCCGAATCA
										CC
chr	503153	C	A	CREL	p.D18	0.035	0.027	4.33	1.29	ACATGGGGT	SEQ
22	63			D2	2E	54	77	E-	[1.09-	ACCAGGGCC	ID
								03	1.53]	CGCTGTGCA	No:
										CTGACTGCA	637
										TGGA[C/A]GG
										CTACTTCAG
										CTCGCTCCG
										GAACGAGAC
										CCACAGCAT
										CT
chr	507212	T	C	PLXN	p.M95	0.009	0.006	2.76	1.47	TTGGGCACG	SEQ
22	52			B2	9V	31	34	E-	[1.06-	GGGGACCCC	ID
								02	2.04]	CCGTAGGAG	No:
										ACCTCCAGA	638
										AGCA[T/C]CT
										GGCCCCGTG
										TCGCCTGGG
										GGCCAGTGA
										CACACTGGA
										GC
chr	126965	G	A	CNTN	p.K11	0.007	0.005	1.83	1.57	GCCTGGCCA	SEQ
3	8			6	3K	84	02	E-	[1.1-	CCAATCTTCT	ID
								02	2.24]	GGGGACAAT	No:
										TCTGAGTCG	639
										GAA[G/A]GC
										AAAGCTCCA
										ATTTGCATG
										TGAGTTTGG
										GGTAAATTT
										TG
chr	109768	C	T	SLC6A	p.C564	0.005	0.003	3.50	1.63	ATGGCATTG	SEQ
3	31			11	C	15	17	E-	[1.05-	GCTGGCTCA	ID
								02	2.53]	TGGCCCTGT	No:
										CCTCCATGC	640
										TCTG[C/T]AT
										CCCGCTCTG
										GATCTGCAT
										CACAGTGTG
										GAAGACGGA
										GG
chr	147246	C	T	C3orf2	p.L26	0.009	0.006	5.92	1.61	ACAGGTTTC	SEQ
3	64			0	L	80	11	E-	[1.17-	AGCAGCAGT	ID
								03	2.22]	CCATCCACC	No:
										TGCTGACGG	641
										AGCT[C/T]CT
										CAGACTGAA
										GATGAAGGC
										CATGGTGGA
										GTCTATGTC
										GG
chr	324094	C	T	CMTM	p.A12	0.008	0.005	1.57	1.54	TGTGCTTTA	SEQ
3	08			8	2A	82	74	E-	[1.1-	ACGGCAGTG	ID
								02	2.16]	CCTTCGTCTT	No:
										GTACCTCTCT	642
										GC[C/T]GCTG
										TTGTAGATG
										CATCTTCCGT
										CTCCCCTGA
										GAGGGACA
chr	367800	C	T	DCLK	p.R24	0.012	0.009	4.43	1.36	TGGAGAAGG	SEQ
3	80			3	Q	50	21	E-	[1.02-	GGCACGGCT	ID
								02	1.81]	GTGCTGGGC	No:
										CAGTGTCAG	643
										GGCC[C/T]GG
										GCTTTGTTG
										GGGTACAGT
										TCTTCTACA
										GCCACCTGA
										AT
chr	383476	C	T	SLC22	p.L55F	0.009	0.006	3.16	1.44	GAGGGCTGT	SEQ
3	80			A14		56	64	E-	[1.04-	CCACACCAA	ID
								02	1.99]	GCAGGATGA	No:
										CAAGTTTGC	644
										CAAC[C/T]TC
										CTGGATGCG
										GTGGGGGAG
										TTTGGCACA
										TTCCAGCAG
										AG
chr	386718	G	A	SCN5A	p.H11	0.005	0.002	2.12	2.01	ATGAGTGAA	SEQ
3	40				8H	88	94	E-	[1.33-	CCAGAATCT	ID
								03	3.05]	TCACAGCCG	No:
										CTCTCCGGA	645
										TGGG[G/A]TG
										GAAGGGACT
										GAGGACATA
										CAAGGCGTT
										GGTGGCACT
										GA
chr	419493	G	A	ULK4	p.P391	0.008	0.005	2.71	1.5[1	TAGGAAGAA	SEQ
3	48				S	58	74	E-	.06-	AATTTCCCA	ID
								02	2.11]	AGTCTGCTC	No:
										ACCTTGGTC	646
										AGAG[G/A]A
										GAAGTCTTC
										TGTGGTGAA
										CAGTGAGTC
										ATATCCTCA
										CCA
chr	427750	G	A	CCDC	p.R471	0.007	0.000	8.25	88.7	CTGGGTCCT	SEQ
3	60			13	R	11	08	E-	2[41.	CCAGGAACT	ID
								35	97-	GGGTATAGG	No:
									187.	CAGGGCTGA	647
									53]	CCTC[G/A]CG
										GCCACTGGA
										CCCCTCACC
										CACTCCTTTA
										TTCCGAAGA
										T
chr	455420	C	T	LARS2	p.A56	0.006	0.003	1.03	2.02	GGATGCCTG	SEQ
3	03				4A	86	41	E-	[1.38-	TGGATTTGT	ID
								03	2.97]	ACATTGGAG	No:
										GGAAAGAAC	648
										ATGC[C/T]GT
										CATGCACTT
										GTTCTATGC
										AAGATTCTT
										TAGTCATTTT
										T
chr	460629	G	A	XCR1	p.S173	0.009	0.005	1.02	1.57	GGAGGTGAG	SEQ
3	22				L	31	97	E-	[1.13-	GTACCACGT	ID
								02	2.17]	GAGTTCGGA	NO:
										ATAATCACA	649
										GCCC[G/A]AA
										GAAAGCACC
										TTGTGGAAG
										ATGGTGTCG
										AGGATGGAG
										GA
chr	464969	G	A	LTF	p.A17	0.007	0.004	2.66	1.55	GGTTGGGGA	SEQ
3	10				4A	11	61	E-	[1.06-	ACTGTCCTTT	ID
								02	2.25]	ATCTGCACC	NO:
										GGGAACACA	650
										GCT[G/A]GCT
										GAGAAGAAC
										CTGGCCACA
										GCTGTTAAA
										CACAGAGAA
										G
chr	495691	G	A	DAG1	p.V41	0.006	0.002	7.27	2.16	CTGGCCAGA	SEQ
3	77				1V	37	96	E-	[1.45-	TTCGCCCAA	ID
								04	3.22]	CGATGACCA	NO:
										TTCCTGGCT	651
										ATGT[G/A]GA
										GCCTACTGC
										AGTTGCTAC
										CCCTCCCAC
										AACCACCAC
										CA
chr	497288	A	G	RNF12	p.E32	0.009	0.006	2.22	1.49	CTTTTCTCCC	SEQ
3	70			3	G	56	43	E-	[1.08-	TTCTGACTTG	ID
								02	2.06]	TGGCTCAGG	NO:
										CATTGTGCA	652
										GG[A/G]GAA
										GCTGCTGAA
										TGACTACCT
										GAACCGCAT
										CTTTTCCTCT
chr	503345	C	T	NAT6	p.V14	0.008	0.005	2.17	1.53	TGGTTCAGC	SEQ
3	40				1I	09	29	E-	[1.07-	ACCCGTGAC	ID
								02	2.18]	AGGCGGGCA	NO:
										TGGCCCACC	653
										ACAA[C/T]GG
										GTGCTGCTT
										CAAGTGTGG
										GGTGGGGGC
										TTAGCAGCA
										TC
chr	520056	G	A	ABHD	p.R8C	0.007	0.005	4.86	1.45	AAGAAGAGG	SEQ
3	65			14B		60	26	E-	[1.01-	GCCTGGCCC	ID
								02	2.08]	TGCACCTGG	No:
										ATGGTGCCC	654
										TCGC[G/A]CT
										GCTCCACGC
										TTGCTGCCA
										TGCCTGCTG
										CTGCTGTGC
										TG
chr	525408	C	T	STAB1	p.S655	0.006	0.004	2.53	1.61	TGCCCCCGA	SEQ
3	42				S	62	12	E-	[1.09-	CCATCCTGC	ID
								02	2.38]	CCATCCTGC	No:
										CCAAGCACT	655
										GCAG[C/T]GA
										GGAGCAGCA
										CAAGATTGT
										GGCGGTGAG
										CCTCGCCTG
										CA
chr	757862	A	G	ZNF71	p.S855	0.005	0.000	1.25	89.9	TTTTCTCCTG	SEQ
3	11			7	P	15	06	E-	2[12.	TGTGTGTTCT	ID
								14	09-	CTGATGTAT	No:
									668.	ACTGAGGCC	656
									7]	TG[A/G]CTTC
										TGGGAGAAA
										GTTTTCCTAC
										ATTCATTAC
										ATCTAAAG
chr	757869	C	A	ZNF71	p.R611	0.008	0.000	1.48	Inf	ACATTCATT	SEQ
3	42			7	I	58	00	E-		ACATTCATA	ID
								41		GGGTCTTTC	No:
										CCCTGTGTG	657
										AGTT[C/A]TC
										TTGTGTATCC
										CAAGGTTTA
										ACTTATTGA
										TAAAGGTTT
										T
chr	757872	G	T	ZNF71	p.P506	0.011	0.000	9.28	Inf	TTACAGCGA	SEQ
3	58			7	T	52	00	E-		AAGGTTTTC	ID
								35		CCACATTCA	No:
										TTGCATTCGT	658
										AGG[G/T]TTT
										TTCCCCTGTG
										TGAGTCCAT
										TGATGGATA
										GTGAGGAAT
chr	757875	G	C	ZNF71	p.L410	0.027	0.000	3.86	Inf	TAGGGCTTT	SEQ
3	46			7	V	45	00	E-		TCCCCTGTGT	ID
								62		GAGTTCTAT	No:
										GATGTATTG	659
										TGA[G/C]GTA
										TGACTTCTG
										GCTAAAGGT
										TTTTCCACAT
										TCACTACAC
chr	757881	G	C	ZNF71	p.L206	0.007	0.000	3.87	Inf	TTGAAGGTT	SEQ
3	58			7	V	35	00	E-		TTCCCTTGTT	ID
								34		CATTACATT	No:
										GAAAAGTCT	660
										GCA[G/C]CAG
										AGTTTGAAT
										CTTGTGATG
										CTGAGTAAG
										ATGTTCATG
										A
chr	757882	T	A	ZNF71	p.D16	0.006	0.000	7.04	14.7	TGTCTCCCC	SEQ
3	92			7	1V	13	42	E-	5[6.0	AGGCTTAAT	ID
								12	4-	AGGGAAAAG	No:
									35.9	CATGTTCTG	661
									7]	GCAA[T/A]CA
										TTAAACTGC
										CCAGGCTTC
										ATTCCTGAA
										CTGTTTCCAT
										T
chr	999985	G	C	p.C31	TBC1	0.008	0.005	4.33	1.45	AGGGAAAAA	SEQ
3	31			D23	S	09	59	E-	[1.02-	GATCTTGAA	ID
								02	2.06]	GAAGCTCTG	No:
										GAAGCAGGA	662
										GGTT[G/C]TG
										ATCTTGAAA
										CGTTGAGAA
										ATATAATTC
										AAGGAAGAC
										CG
chr	113052	G	C	WDR5	p.P118	0.006	0.004	4.42	1.5[1	TTCCTCTTCC	SEQ
3	314			2	5R	86	57	E-	.02-	TTCTTGGCA	ID
								02	2.23]	GCATTTATTC	No:
										TCATGTGCT	663
										CA[G/C]GTAT
										CTTGTAGTCT
										GGGGCTGTC
										TTCAGATTG
										AAATCTCC
chr	124578	C	G	ITGB5	p.E80	0.009	0.006	3.42	1.45	GGCAGGCTC	SEQ
3	212				Q	07	25	E-	[1.04-	CTCAGGACA	ID
								02	2.03]	TGGAAGCTG	No:
										CTGGCTGGG	664
										CTCT[C/G]TA
										TCTCACCTCC
										ACAGCCATT
										TTTGACAAG
										GTTTGCCCTC
chr	124646	G	A	MUC1	p.T66I	0.006	0.004	3.25	1.59	GGAGGAACT	SEQ
3	693			3		37	03	E-	[1.07-	ATGTGTACT	ID
								02	2.36]	AATTATGGG	No:
										GGGAGCAGG	665
										TGAA[G/A]TA
										GCTGTTGGG
										AAAGGTGTA
										TTTGCTGTG
										GTGCTAGCA
										GT
chr	129196	C	T	IFT122	p.R366	0.008	0.005	3.60	1.46	CTATGAGTT	SEQ
3	984				W	33	73	E-	[1.03-	GTATTCAGA	ID
								02	2.06]	GGACTTATC	No:
										AGACATGCA	666
										TTAC[C/T]GG
										GTAAAGGAG
										AAGATTATC
										AAGAAGTTT
										GAGTGCAAC
										CT
chr	132198	G	A	DNAJ	p.R912	0.006	0.003	1.75	1.68	ATTTATTTCA	SEQ
3	097			C13	R	13	65	E-	[1.12-	ATAGTGCAC	ID
								02	2.53]	AGATAAACT	No:
										TGAACGAGA	667
										TAG[G/A]TTG
										ATTCTCTTCC
										TTAACAAGT
										TGATCCTTA
										ATAAGGTAC
chr	132247	T	G	DNAJ	p.L217	0.006	0.004	1.27	1.68	GCTCAGATT	SEQ
3	160			C13	0W	86	09	E-	[1.15-	GTTAAAGCT	ID
								02	2.47]	CTCAAGGCA	No:
										ATGACTCGA	668
										AGTT[T/G]GC
										AGTATGGAG
										AACAGGTGA
										GTCTGCATA
										GAGTCAACT
										TT
chr	136664	A	T	NCK1	p.S139	0.011	0.008	4.08	1.38	AAGTGTTGC	SEQ
3	807				S	03	02	E-	[1.02-	ATGTGGTAC	ID
								02	1.86]	AGGCTCTTT	No:
										ACCCATTCA	669
										GCTC[A/T]TC
										TAATGATGA
										AGAACTTAA
										TTTCGAGAA
										AGGAGATGT
										AA
chr	137849	G	T	A4GN	p.P97P	0.008	0.005	2.16	1.52	TTGCTGACA	SEQ
3	808			T		82	83	E-	[1.08-	GGAAGGAAA	ID
								02	2.13]	AAGCTGGGT	No:
										ATGTGGAGT	670
										TTGA[G/T]GG
										CATCGGTGT
										GGAATCAGT
										AAGACCCTT
										CATAAAGAA
										CA
chr	186953	C	T	MASP	p.P582	0.009	0.005	1.70	1.54	AGATGCCCC	SEQ
3	913			1	P	07	90	E-	[1.11-	AGCCGGCCA	ID
								02	2.15]	CCAGGCCCA	No:
										GCATGTGGG	671
										GGGC[C/T]GG
										GCCTTCAGG
										CTCAAGCCT
										TGGCAGGCA
										GACAGGCAT
										AA
chr	192980	C	T	HRASL	p.S160	0.008	0.005	7.49	1.64	AATTCTACTT	SEQ
3	784			S	S	33	09	E-	[1.16-	TATAGATGG	ID
								03	2.33]	CATTCCTGC	NO:
										GTCCTTTAC	672
										AAG[C/T]GCC
										AAGTCTGTA
										TTCAGCAGT
										AAGGCCCTG
										GTGAAAATG
										C
chr	195306	A	G	APOD	p.F15S	0.009	0.005	9.46	1.59	GCACTTCCC	SEQ
3	289					31	89	E-	[1.14-	AAGATGAAA	ID
								03	2.2]	TGCTTGTCCC	NO:
										TCTGCCGCA	673
										CCG[A/G]AG
										AGGCCAGCC
										AGTGCGGAA
										AGCAGCAGC
										AGCAGCATC
										AC
chr	195505	C	G	MUC4	p.V42	0.025	0.000	6.23	Inf	GGGGTGGCG	SEQ
3	772				27L	74	00	E-		TGACCTGTG	ID
								146		GATACTGAG	No:
										GAAAGGCTG	674
										GTGA[C/G]AG
										GAAGAGGGG
										TGGCGTGAC
										CTGTGGATG
										CTGAGGAAG
										TG
chr	195508	G	C	MUC4	p.L342	0.009	0.000	2.06	51.1	GCGTGACCG	SEQ
3	178				5V	80	19	E-	6[26.	GTGGATGCT	ID
								37	23-	GAGGAAGTG	No:
									99.7	CTGGTGACA	675
									9]	GGAA[G/C]A
										GGGGTGGCG
										TGACCTGTG
										GATGCTGAG
										GAAGGGCTA
										GTG
chr	195508	T	G	MUC4	p.T341	0.016	0.000	6.58	38.6	CTGAGGAAG	SEQ
3	194				9T	42	43	E-	[24.1	TGCTGGTGA	ID
								58	9-	CAGGAAGAG	NO:
									61.5	GGGTGGCGT	676
									9]	GACC[T/G]GT
										GGATGCTGA
										GGAAGGGCT
										AGTGACAGG
										AAGAGGCAT
										GG
chr	195512	T	C	MUC4	p.S205	0.015	0.000	2.79	68.2	GGAAGAGGC	SEQ
3	294				3G	20	23	E-	6[37.	GTGGTGTCA	ID
								60	51-	CCTGTGGAT	NO:
									124.	ACTGAGGAA	677
									21]	AGGC[T/C]GG
										TGACAGGAA
										GAGGGGTGT
										CCTGACCTG
										TGGATGCTG
										AG
chr	195512	C	G	MUC4	p.Q20	0.011	0.000	1.51	32.7	TGGATACTG	SEQ
3	316				45H	27	35	E-	1[19.	AGGAAAGGC	ID
								38	15-	TGGTGACAG	NO:
									55.8	GAAGAGGGG	678
									8]	TGTC[C/G]TG
										ACCTGTGGA
										TGCTGAGGA
										AGTATCGGT
										GACAGGAAG
										CG
chr	195512	G	A	MUC4	p.P182	0.011	0.000	3.64	352	TCACCTGTG	SEQ
3	981				4S	52	03	E-	[85.4	GATGCTGAG	ID
								54	7-	GAAGCGTCG	NO:
									1449	GTGACAGGA	679
									.66]	AGAG[G/A]G
										GTGGTGTCA
										CCTGTGGAT
										GCTGAGGAA
										GGGCTGGTG
										ACA
chr	196214	C	T	RNF16	p.R164	0.023	0.000	6.42	388.	GTTCCTCATC	SEQ
3	336			8	R	77	06	E-	53[1	ACTTTTCAGT	ID
								132	80.3-	TGTTCTTCCA	No:
									837.	TCGCTCTTCG	680
									21]	[C/T]CTTTTTT
										CTGCCTGTCT
										TTTTTCCTCT
										TCTTCCTCCT
										CTG
chr	196214	T	C	RNF16	p.R164	0.009	0.000	1.81	Inf	TCCTCATCA	SEQ
3	338			8	G	56	00	E-		CTTTTCAGTT	ID
								57		GTTCTTCCAT	NO:
										CGCTCTTCG	681
										CC[T/C]TTTT
										TCTGCCTGTC
										TTTTTTCCTC
										TTCTTCCTCC
										TCTGCC
chr	265813	A	T	ZNF73	p.F277	0.022	0.000	2.19	492.	TGAGGATGA	SEQ
4				2	Y	30	05	E-	83[2	GGTAATGAT	ID
								124	00.2-	TTTGCCACA	NO:
									1213	TTCTTCACAT	682
									.19]	GTG[A/T]AGG
										GTTTCTCTTC
										AGCATGAAT
										TCTCTTATGC
										TTAGTAAG
chr	265825	T	C	ZNF73	p.E273	0.011	0.000	2.01	Inf	AATGATTTT	SEQ
4				2	G	52	00	E-		GCCACATTC	ID
								68		TTCACATGT	No:
										GAAGGGTTT	683
										CTCT[T/C]CA
										GCATGAATT
										CTCTTATGCT
										TAGTAAGGG
										TTGAGGACC
										T
chr	265829	C	T	ZNF73	p.A27	0.018	0.000	1.83	Inf	ATTTTGCCA	SEQ
4				2	2T	14	00	E-		CATTCTTCAC	ID
								107		ATGTGAAGG	No:
										GTTTCTCTTC	684
										AG[C/T]ATGA
										ATTCTCTTAT
										GCTTAGTAA
										GGGTTGAGG
										ACCTATTA
chr	436337	G	A	ZNF72	p.P640	0.008	0.000	4.30	Inf	TGATGGGGC	SEQ
4				1	L	82	00	E-		AAAGGCTTT	ID
								53		GCCACACTC	No:
										TTCACATTTG	685
										TAA[G/A]GTT
										TCTCCCCAG
										TGTAAATTTT
										CTTCTGTTGA
										TTCAGGTC
chr	436390	A	G	ZNF72	p.F622	0.005	0.000	3.07	660.	TGTAAATTTT	SEQ
4				1	F	88	01	E-	68[8	CTTCTGTTGA	ID
								34	9.36-	TTCAGGTCC	No:
									4884	GTGTACCAT	686
									.86]	AC[A/G]AAGT
										CTTTGCCAC
										ACTCTTCAC
										ATTTGTAAA
										GTTTCTCTC
chr	437293	A	G	ZNF72	p.Y32	0.013	0.000	1.88	103.	ATGTGTAGG	SEQ
4				1	1Y	73	13	E-	33[5	GTTTCTCTCC	ID
								67	8.4-	AGTATGAAT	No:
									182.	TCTCCTATGT	687
									84]	AC[A/G]TAAA
										GGTTTGCGG
										ACTGTCTAA
										AGGCTTTGC
										CACATACTT
chr	676125	G	C	MFSD	p.S434	0.007	0.004	9.52	1.71	GGCGCCGGT	SEQ
4				7	R	11	18	E-	[1.16-	ATGGGGTGT	ID
								03	2.51]	GGAAGAAGA	No:
										CCGCCAGGA	688
										TGCA[G/C]CT
										GAAGAAGGT
										GCACAGGCC
										GGCCATCAG
										CAGCAGAGA
										CA
chr	138836	G	A	CRIPA	p.A24	0.006	0.000	1.22	109.	GGAGTGCCC	SEQ
4	9			K	T	86	06	E-	46[4	GCCTGCTCA	ID
								34	7.78-	CACGTGCCC	No:
									250.	ATGTGGAGT	689
									72]	GCCC[G/A]CC
										TGCTCATGT
										GCCCATGTG
										GAGTGCCCG
										CCTGCTCAC
										AC
chr	138941	C	T	CRIPA	p.P373	0.006	0.000	5.30	238.	GAGTGCCCG	SEQ
4	7			K	L	37	03	E-	42[7	CCTGCTCAC	ID
								35	2.13-	ACACGTGCC	NO:
									788.	CATGTGGAG	690
									02]	TGCC[C/T]GC
										CTGCTCACA
										CGTGCCCAT
										GTGGAGTGC
										CTGCCTGCT
										CA
chr	180550	C	T	FGFR	p.T338	0.007	0.003	1.52	1.9[1	CCTTGCACA	SEQ
4	2			3	T	35	89	E-	.31-	ACGTCACCT	ID
								03	2.75]	TTGAGGACG	NO:
										CCGGGGAGT	691
										ACAC[C/T]TG
										CCTGGCGGG
										CAATTCTATT
										GGGTTTTCTC
										ATCACTCTG
chr	341781	C	T	RGS12	p.A14	0.010	0.006	1.19	1.52	ATCGACAGC	SEQ
4	1				9V	29	78	E-	[1.11-	CAGGCCCAG	ID
								02	2.08]	CTAGCAGAC	NO:
										GACGTCCTC	692
										CGCG[C/T]AC
										CTCACCCAG
										ACATGTTCA
										AGGAGCAGC
										AGCTGCAGG
										TA
chr	351988	C	T	LRPAP	p.D21	0.005	0.003	4.80	1.62	AGCTCCGTG	SEQ
4	1			1	1N	15	19	E-	[1.04-	TGCCTGCTG	ID
								02	2.51]	TGCAGGACG	NO:
										CTGCCCTTG	693
										ATGT[C/T]GC
										TCAGGTCCG
										AGGGGCTAA
										TGACGTTCT
										CGTGGATTT
										CT
chr	700663	G	C	TBC1	p.E166	0.006	0.004	2.71	1.58	AGCCAAGGA	SEQ
4	6			D14	Q	62	20	E-	[1.07-	GAGGTGGCG	ID
								02	2.33]	GTCCCTTAG	NO:
										CACAGGAGG	694
										CTCT[G/C]AA
										GTGGAGAAC
										GAAGGTAGA
										ATGTCTTCTA
										AAACCAGCG
										G
chr	135457	C	G	NKX3-	p.A11	0.005	0.000	8.15	Inf	CCGAGGCTC	SEQ
4	02			2	3P	15	00	E-		AAGGATCCC	ID
								28		CCCGCAAGG	NO:
										CCGGCCCCG	695
										CTGG[C/G]CC
										CCCGCGCGT
										CCGCGCAGC
										GCCGCCTGC
										TCTCGTTCTC
										C
chr	165042	T	G	LDB2	p.N36	0.020	0.000	1.23	2373	CTGGTGCCG	SEQ
4	91				6T	83	01	E-	.68[3	ATCATCTTAT	ID
								122	30.4	TGGGAAGCC	NO:
									6-	TGGGGTGGG	696
									1705	GGG[T/G]TTT
									0.06]	CTGATTTGG
										TCTCTTGAGT
										GGCGGGAGG
										TTTACTGTT
chr	577972	A	G	REST	p.I747	0.010	0.000	4.04	Inf	CTCCTCCCAT	SEQ
4	65				M	05	00	E-		GGAGGTGGT	ID
								60		CCAGAAGGA	No:
										GCCTGTTCA	697
										GAT[A/G]GA
										GCTGTCTCCT
										CCCATGGAG
										GTGGTCCAG
										AAGGAACCT
										G
chr	629360	C	A	LPHN	p.N12	0.006	0.004	3.32	1.65	GTGAACAGA	SEQ
4	92			3	92K	831	163	E-	[1.01-	ACAGGAATC	ID
								02	2.55]	TGATGAACA	NO:
										AGCTGGTGA	698
										ATAA[C/A]CT
										TGGCAGTGG
										AAGGGAAGA
										TGATGCCAT
										TGTCCTGGA
										TG
chr	694337	T	A	UGT2	p.D14	0.009	0.006	1.90	1.48	CAGCTCACC	SEQ
4	63			B17	7V	80	63	E-	[1.08-	ACAGGGATT	ID
								02	2.04]	AACGGCATC	NO:
										TGCCAGAAG	699
										GACA[T/A]CA
										AATTTTGAC
										TCTTGTAGTT
										TTCTCATAA
										GTTTCTTGTT
chr	698747	T	C	UGT2	p.T134	0.010	0.000	4.99	27.9	AACAATGGA	SEQ
4	38			B10	A	78	39	E-	[18.3	ATGCCCACC	ID
								40	1-	ATAGGGATC	NO:
									42.5	CCATGGTAG	700
									3]	ATTGCT
										CGTAGATGC
										CATTGGCTC
										CACCATGAG
										TTATAAAAG
										CT
chr	698747	G	A	UGT2	p.Y13	0.011	0.000	1.22	26.1	ATGGAATGC	SEQ
4	42			B10	2Y	76	45	E-	7[17.	CCACCATAG	ID
								42	59-	GGATCCCAT	NO:
									38.9	GGTAGATTG	701
									4]	TCTC[G/A]TA
										GATGCCATT
										GGCTCCACC
										ATGAGTTAT
										AAAAGCTCT
										GG
chr	712325	C	A	SMR3	p.S79	0.007	0.000	8.43	Inf	CCCCTTTCTC	SEQ
4	42			A	Y	60	00	E-		CACCCTATG	ID
								46		GTCCAGGGA	NO:
										GAATCCCAC	702
										CAT[C/A]CCC
										TCCTCCACC
										CTATGGTCC
										AGGGAGAAT
										TCAATCACA
										C
chr	723385	A	G	SLC4A	p.K60	0.007	0.003	7.37	2.04	TCCTCTCTGA	SEQ
4	89			4	2R	11	50	E-	[1.4-	TTAGCTTCAT	ID
								04	2.98]	CTTTATCTAT	NO:
										GATGCTTTC	703
										A[A/G]GAAG
										ATGATCAAG
										CTTGCAGAT
										TACTACCCC
										ATCAACTCC
chr	772045	C	T	FAM4	p.R283	0.010	0.006	1.10	1.54	TTAGTTCCTT	SEQ
4	70			7E	C	29	72	E-	[1.12-	GAGAATATG	ID
								02	2.12]	TATATCGGG	NO:
										AAGGAATGT	704
										AAA[C/T]GTG
										CATGTAATA
										AGACTCCTA
										TAAAACGAA
										CTCAAGCAT
										A
chr	797921	G	A	BMP2	p.Q48	0.012	0.000	1.06	1376	AACAGCAAC	SEQ
4	48			K	1Q	75	01	E-	.85[1	AGCAGCAGC	ID
								73	90.3-	AGCAACAGC	NO:
									9961	AACAGCAGC	705
									.91]	AGCA[G/A]C
										AGCAGCAGC
										AGCAGCACC
										ACCACCACC
										ACCACCACC
										ACC
chr	819672	C	T	BMP3	p.T222	0.000	0.000	1.00	0.79	GCCAAAGAA	SEQ
4	40				M	49	62	E+0	[0.19-	AATGAAGAG	ID
								0	3.22]	TTCCTCATA	NO:
										GGATTTAAC	706
										ATTA[C/T]GT
										CCAAGGGAC
										GCCAGCTGC
										CAAAGAGGA
										GGTTACCTTT
										T
chr	876662	A	G	PTPN1	p.H86	0.009	0.005	1.49	1.77	AAGATATGC	SEQ
4	25			3	5R	31	28	E-	[1.27-	CAGTACCTG	ID
								03	2.46]	CTGCACCTC	NO:
										TGCTCTTACC	707
										AGC[A/G]TAA
										GTTCCAGCT
										ACAGATGAG
										AGCAAGACA
										GAGCAACCA
										A
chr	876722	G	T	PTPN1	p.D10	0.008	0.005	9.90	1.61	GAGTTTAAA	SEQ
4	35			3	42Y	82	50	E-	[1.15-	TAGAAGTCC	ID
								03	2.26]	TGAAAGGAG	NO:
										GAAACATGA	708
										ATCA[G/T]AC
										TCCTCATCC
										ATTGAAGAC
										CCTGGGCAA
										GCATATGTT
										CT
chr	877491	G	A	SLC10	p.H24	0.028	0.000	2.75	Inf	AGTTTATGG	SEQ
4	62			A6	9Y	68	00	E-		ATAGTTTAA	ID
								171		CTATACCTTT	NO:
										GCCAAGACT	709
										GGT[G/A]GGT
										AAAAAGTGC
										CAGCAGAAA
										ACCCGTGAC
										ATGGCCAAT
										C
chr	885375	C	T	DSPP	p.S124	0.010	0.000	3.86	Inf	AAAGCAGCG	SEQ
4	52				6S	78	00	E-		ACAGCAGTG	ID
								52		ACAGCAGCG	NO:
										ATAGCAGTG	710
										ACAG[C/T]AG
										CAACAGCAG
										TGACAGCAG
										CGACAGCAG
										TGATAGCAG
										TG
chr	885375	C	T	DSPP	p.N12	0.011	0.000	5.36	54.1	GCGACAGCA	SEQ
4	58				48N	52	22	E-	4[28.	GTGACAGCA	ID
								43	06-	GCGATAGCA	No:
									104.	GTGACAGCA	711
									46]	GCAA[C/T]AG
										CAGTGACAG
										CAGCGACAG
										CAGTGATAG
										CAGTGACAG
										CA
chr	113303	A	G	ALPK1	p.Q67	0.011	0.007	2.92	1.61	GCAAAGGAA	SEQ
4	632				R	76	35	E-	[1.2-	ATGAAGTGG	ID
								03	2.15]	CCCTTCGTG	NO:
										CCTGAAAAG	712
										TGGC[A/G]GT
										ACAAACAAG
										CCGTGGGCC
										CAGAGGACA
										AAACAAACC
										TG
chr	115997	T	C	NDST4	p.I283	0.012	0.009	3.24	1.37	AGCCTCTTC	SEQ
4	346				V	75	37	E-	[1.03-	CCTGACAAG	ID
								02	1.81]	AAGGAGATG	NO:
										GCATCTATG	713
										AAGA[T/C]GA
										GCTTGTGCA
										GCCAAAAGT
										TCAAGTTGT
										TGCCAAAAA
										GT
chr	125592	G	A	ANKR	p.A52	0.011	0.008	3.46	1.39	CATTATCTA	SEQ
4	869			D50	1A	27	16	E-	[1.03-	ATAATGTCC	ID
								02	1.87]	GAATGGAAT	No:
										CCTCTCTTTC	714
										TAA[G/A]GCT
										TGTCGAACT
										ATGCATGAT
										GTGCGATCG
										TCTTCACTGT
chr	153690	G	A	TIGD4	p.T477	0.005	0.003	1.38	1.74	ATCTTGACTT	SEQ
4	727				I	88	39	E-	[1.15-	CTGAGAAAT	ID
								02	2.63]	TTTTTCAGA	No:
										GTATCTAAA	715
										GCA[G/A]TTA
										TTGCCTCAG
										ATTTTGATG
										GTAAAGGGA
										GTTCAGTTC
										C
chr	165962	A	T	TRIM6	p.E422	0.006	0.003	2.13	1.64	TAGTAAAAC	SEQ
4	490			0	D	37	89	E-	[1.11-	CCAGTAAAA	ID
								02	2.45]	TTGGTATTTT	No:
										TCTGGACTA	716
										TGA[A/T]TTG
										GGTGATCTT
										TCCTTTTATA
										ATATGAATG
										ATAGGTCTA
chr	166300	T	C	CPE	p.F51L	0.005	0.000	4.59	Inf	GAGGCGGCG	SEQ
4	524					15	00	E-		CCGGCGGCT	ID
								30		GCAGCAAGA	No:
										GGACGGCAT	717
										CTCC[T/C]TC
										GAGTACCAC
										CGCTACCCC
										GAGCTGCGC
										GAGGCGCTC
										GT
chr	167656	A	T	SPOC	p.X31	0.003	not	5.64	Inf	TTAGAAATG	SEQ
4	074			K3	7R	93	found	E-		TAGAATTTA	ID
								08		TTGATTTCA	No:
										ACTGTCATC	718
										AATC[A/T]AA
										TGTATACAT
										CATGGTCAT
										CACCACCAT
										CATCATCAT
										CC
chr	170671	C	G	C4orf2	p.G82	0.005	0.003	4.94	1.6[1	TTCTTCGTTT	SEQ
4	841			7	R	15	23	E-	.03-	TATGTTTTCC	ID
								02	2.48]	AGCAAGGAT	No:
										ATCATAAGG	719
										AC[C/G]AACT
										AATTGAAGT
										CCAAGGCTT
										GCAGAAAGT
										GAATCTATA
chr	175898	T	C	ADAM	p.W73	0.006	0.000	1.43	33.5	TCAGCGTCG	SEQ
4	879			29	5R	37	19	E-	3[18.	ACCTCATGA	ID
								25	85-	GTTACCTCC	No:
									59.6	CCAGAGTCA	720
									3]	ACCT[T/C]GG
										GTGATGCCT
										TCCCAGAGT
										CAACCTCCT
										GTGACGCCT
										TC
chr	175898	C	T	ADAM	p.S757	0.006	0.000	7.49	12.9	CTGTGACGC	SEQ
4	947			29	S	62	52	E-	1[8.1	CTTCCCAGA	ID
								19	6-	GTCATCCTC	No:
									20.4	AGGTGATGC	721
									2]	CTTC[C/T]CA
										GAGTCAACC
										TCCTGTGAC
										ACCCTCCCA
										GAGTCAACC
										TC
chr	177083	G	A	WDR1	p.D93	0.006	0.004	1.23	1.7[1	GCACAAAGT	SEQ
4	272			7	3N	86	05	E-	.16-	CAGTAAAGA	ID
								02	2.49]	ACTGGCAGA	No:
										ATGGTATTTT	722
										CAA[G/A]ATG
										GTCGAGCAG
										TACTAGCCG
										CATGTTGCC
										ATCTTGCCA
										T
chr	191718	C	G	LRRC1	p.A22	0.008	0.000	8.74	Inf	TTCATTTCTG	SEQ
5				4B	G	82	00	E-		CAGAAGCTC	ID
								53		TGGTGTCCC	No:
										ACCCCCAGG	723
										TGG[C/G]CCG
										GCAGAGCCT
										GGACAGCGT
										GGCCCACAA
										CCTCTACCC
										A
chr	891400	T	C	BRD9	p.K39	0.000	0.001	5.63	10[5	CCGTGTCAC	SEQ
5					R	90	70	E-	-21]	AGTGCTCCC	ID
								09		TCTCTCGCTT	No:
										CCGCTTCTTC	724
										TC[T/C]TCCT
										GGGCGGCAG
										AGTCAAGGG
										AGTGAGAAA
										GGCAGGAGT
chr	739660	T	G	ADCY	p.F65	0.008	0.000	3.47	Inf	GCTCATCGT	SEQ
5	2			2	V	58	00	E-		CATGGGCTC	ID
								49		CTGCCTCGC	No:
										CCTGCTCGC	725
										CGTC[T/G]TC
										TTCGCGCTC
										GGGCTGGTG
										AGTGGCCTC
										CCCGCGGGT
										CC
chr	369854	G	A	NIPBL	p.G72	0.005	0.000	9.80	628.	GTGAAAGCC	SEQ
5	42				0G	64	01	E-	63[8	GGCCTGAGA	ID
								33	4.88-	CTCCAAAAC	No:
									4655	AAAAGAGTG	726
									.98]	ATGG[G/A]CA
										TCCTGAAAC
										CCCAAAACA
										GAAGGGTGA
										TGGAAGGCC
										TG
chr	523473	A	C	ITGA2	p.T252	0.008	0.005	2.65	1.51	CATCCCAGA	SEQ
5	66				T	58	69	E-	[1.07-	CATCCCAAT	ID
								02	2.13]	ATGGTGGGG	No:
										ACCTCACAA	727
										ACAC[A/C]TT
										CGGAGCAAT
										TCAATATGC
										AAGGTAAGT
										TTTGGTGCT
										AA
chr	550836	G	T	DDX4	p.A19	0.005	0.000	2.43	603.	GCAACTTAA	SEQ
5	98				9S	39	01	E-	79[8	CTTCTAGGC	ID
								31	1.37-	GGCTTTTCTC	No:
									4480	CTACCAATT	728
									.44]	TTG[G/T]CTC
										ATATGATGC
										ATGATGGAA
										TAACTGCCA
										GTCGTTTTA
										A
chr	708062	C	A	BDP1	p.G11	0.008	0.000	1.09	Inf	TGGAAGAAA	SEQ
5	31				04G	09	00	E-		CTGAAAGAG	ID
								48		AAATATCCC	No:
										CACAGGAAA	729
										ATGG[C/A]CT
										AGAGGAGGT
										TAAGCCTCT
										AGGTGAAAT
										GCAAACAGA
										TT
chr	715167	G	C	MRPS	p.Q39	0.005	0.003	3.05	1.68	GCTTTCTGA	SEQ
5	95			27	6E	15	06	E-	[1.08-	GCCTGGTAC	ID
								02	2.62]	TCCTGCTTCG	No:
										CTTGCTCCCT	730
										CT[G/C]TTGC
										TGTTCTCTCT
										GGATCAACT
										GTACAAGGT
										CTAGATGC
chr	762495	G	A	CRHB	p.P53P	0.010	0.007	4.12	1.4[1	TCAGCGCCA	SEQ
5	03			P		29	39	E-	.02-	ACCTGAAGC	ID
								02	1.91]	GGGAGCTGG	No:
										CTGGGGAGC	731
										AGCC[G/A]TA
										CCGCCGCGC
										TCTGCGTGA
										GTCGAGGCT
										GCCCGGCTC
										GC
chr	762498	A	AC	CRHB	NM_	0.006	not	7.44	223.	GCTGCAGCC	SEQ
5	52			P	001882:	87	found	E-	6?46.	CGGGACTTA	ID
					exon3:			12	4-	TTGCCCCAT	No:
					c.176-				1077	GCCCTCCTC	732
					2- > C				.6?	CCCC[A/AC]G
										GGTGCCTGG
										ACATGCTGA
										GCCTCCAGG
										GCCAGTTCA
										CCT
chr	767606	C	T	WDR4	p.G61	0.005	0.003	3.47	1.62	ACACACCTG	SEQ
5	20			1	D	88	65	E-	?1.07-	GGCATTCCA	ID
								02	2.44?	CACAACTAC	No:
										AATTCCATC	733
										ATCA[C/T]CA
										GCAGATGCA
										AATCTGGTT
										AGGGAGAAA
										GGGTCAAGA
										AA
chr	798548	A	G	ANKR	p.V33	0.005	0.003	2.71	1.65	AAATATTGT	SEQ
5	26			D34B	8A	39	28	E-	?1.07-	CTGGTTAGA	ID
								02	2.54?	ATCTGGGTC	No:
										CTGGTCAAC	734
										AGGG[A/G]CT
										TCAATGCAT
										TGCTGATTTC
										CTTCTGAAA
										GATAAGATT
										G
chr	899698	A	G	GPR98	p.I164	0.010	0.006	2.82	1.44	GCTTAGTGC	SEQ
5	80				7V	05	98	E-	[1.05-	CTCTGGATA	ID
								02	1.98]	TTTATATTTT	No:
										TAGGTTCTG	735
										AAT[A/G]TAT
										ATGTTCTTG
										ATGATGATA
										TTCCTGAAC
										TTAATGAGT
										A
chr	899795	G	A	GPR98	p.D19	0.009	0.005	6.02	1.64	TATCACTGT	SEQ
5	68				44N	31	69	E-	[1.18-	GGAGATATT	ID
								03	2.28]	GCCTGACGA	No:
										AGACCCAGA	736
										ACTG[G/A]AT
										AAGGCATTC
										TCTGTGTCA
										GTCCTCAGT
										GTTTCCAGT
										GG
chr	929210	C	T	NR2F1	p.H97	0.029	0.000	1.83	838.	TCGAGTGCG	SEQ
5	20				H	66	04	E-	44[3	TGGTGTGCG	ID
								169	09.5	GGGACAAGT	No:
									1-	CGAGCGGCA	737
									2271	AGCA[C/T]TA
									.28]	CGGCCAATT
										CACCTGCGA
										GGGCTGCAA
										AAGTTTCTTC
										A
chr	134002	G	C	SEC24	p.A22	0.013	0.000	5.18	1523	TCATGGGCC	SEQ
5	614			A	3P	48	01	E-	.15[2	CCCTCCAGC	ID
								79	10.7	TGGAGGCCC	NO:
									3-	ACCCCCAGT	738
									1100	GAGG[G/C]CC
									9.22]	CTCACGCCC
										CTGACATCA
										TCATATAGA
										GATGTACCC
										CA
chr	137621	C	T	CDC2	p.R388	0.006	0.003	2.71	1.63	TCATGGGCT	SEQ
5	421			5C	Q	13	76	E-	[1.09-	CATGTCCTTC	ID
								02	2.45]	ACCAGAAGG	NO:
										GCAATCTGC	739
										TCC[C/T]GCA
										GCTGCCGCT
										CCCCTTCCTG
										CACTTTGCTC
										TGGCTTCG
chr	140209	G	A	PCDH	p.R498	0.006	0.004	3.84	1.55	AGGAGAACG	SEQ
5	170			A6	R	62	29	E-	[1.05-	CGCTGGTGT	ID
								02	2.28]	CCTACTCGC	NO:
										TGGTGGAGC	740
										GGCG[G/A]GT
										GGGCGAGCG
										CGCGTTGTC
										GAGCTACAT
										TTCGGTGCA
										CG
chr	140559	T	C	PCDH	p.L576	0.007	0.003	8.04	2.02	CTGTACCCG	SEQ
5	342			B8	P	11	53	E-	[1.38-	CTGCAGAAT	ID
								04	2.95]	GGCTCCGCG	NO:
										CCCTGCACC	741
										GAGC[T/C]GG
										TGCCCCGGG
										CGGCCGAGC
										CGGGCTACC
										TGGTGACCA
										AG
chr	141336	G	A	PCDH	p.T261	0.009	0.005	7.37	1.6[1	GCCTTGGTC	SEQ
5	635			12	M	56	98	E-	.16-	AGGGTCTGT	ID
								03	2.22]	GGCGGTCAG	NO:
										TTTTATGAG	742
										AAGC[G/A]TA
										CCAGGTGCA
										GCATCTTCTT
										GGATTTCCA
										GTGCCAGTG
										A
chr	141694	G	T	SPRY4	p.S218	0.014	0.001	2.15	11.5	GCAGTTGGA	SEQ
5	021				Y	31	26	E-	[7.94-	GCGGGAGCA	ID
								28	16.4	GGAGCAGGG	NO:
									1]	GTGGTCAGC	743
										GCAG[G/T]AG
										CCCTCATCG
										TCCTCATTCG
										TGCAGTGGT
										AGAAGATGC
										C
chr	148384	T	A	SH3TC	p.D12	0.007	0.004	2.62	1.84	GACCGCTGC	SEQ
5	455			2	29V	35	02	E-	[1.27-	TGCCAGGGC	ID
								03	2.66]	CAGAAGGAA	No:
										GTACTCAGT	744
										GGCA[T/A]CA
										TGGGCATCC
										TAACCCCGT
										GGTATGGGG
										GCAAAGAAG
										AG
chr	149276	T	G	PDE6	p.Q49	0.019	0.001	8.09	11.3	ATTTATTAAT	SEQ
5	063			A	2H	52	76	E-	2[8.1	TTCGTATTTA	ID
								37	7-	TCTGCATCT	No:
									15.5	GGCAGCTCC	745
									51]	GC[T/G]TGCT
										GTATAAGGA
										ATAGAGTCA
										GGTGATTAG
										GAAACATGA
chr	149301	G	A	PDE6	p.P293	0.007	0.004	3.83	1.5[1	CCTGGGACC	SEQ
5	253			A	L	11	75	E-	.03-	AGAGTAAGG	ID
								02	2.18]	TGGAACTTC	No:
										ACCCATCAG	746
										AACC[G/A]GC
										CACACATCA
										AAAAATTCC
										TAGGAATGA
										GAAAAACAA
										TA
chr	149512	C	T	PDGF	p.V31	0.006	0.004	1.88	1.64	TCAGCAAAT	SEQ
5	494			RB	6M	86	19	E-	[1.11-	TGTAGTGTG	ID
02	2.43								2.43]	CCCACCTCT	No:
										CCCAGGAGC	747
										CGCA[C/T]GT
										AGCCGCTCT
										CTGCAAGGG
										GTGACCGTC
										AGGGGCGGG
										GC
chr	150905	G	T	FAT2	p.P347	0.006	0.000	4.42	Inf	CCTCCTGCTT	SEQ
5	399				9Q	13	00	E-		AGGCCCTCA	ID
								37		GCAGTCACC	No:
										AGCCATCCA	748
										TCC[G/T]GGG
										TCACTCGGA
										AGGCAGAGC
										CGTTGTTCCC
										CTTGGTGAT
chr	167689	C	A	TENM	p.R257	0.005	0.003	2.93	1.71	CATCATTGG	SEQ
5	228			2	1R	15	02	E-	[1.1-	CAAAGGCAT	ID
								02	2.66]	CATGTTTGC	No:
										CATCAAAGA	749
										AGGG[C/A]G
										GGTGACCAC
										GGGCGTGTC
										CAGCATCGC
										CAGCGAAGA
										TAG
chr	167881	A	T	WWC1	p.E862	0.011	0.000	5.03	Inf	GAGAATGAG	SEQ
5	032				V	76	00	E-		GCAGTAGCC	ID
								70		GAGGAAGAG	NO:
										GAGGAGGAG	750
										GTGG[A/T]GG
										AGGAGGAGG
										GAGAAGAGG
										ATGTTTTCAC
										CGAGAAAGC
										C
chr	168112	G	A	SLIT3	p.A11	0.005	0.002	1.12	2.16	AAGGGCAGG	SEQ
5	707				80A	64	62	E-	[1.41-	GCAGGGCGG	ID
								03	3.31]	GACACACCT	NO:
										GCAGGGAGA	751
										TGTT[G/A]GC
										CTGGGGTCG
										GACCTTGGC
										GGAGGCCAG
										TTCCACGTA
										GG
chr	171661	T	C	UBTD	p.A89	0.009	0.006	3.47	1.45	CATGTGGTA	SEQ
5	166			2	A	07	28	E-	[1.04-	ATGTTATGTT	ID
								02	2.02]	TGCACCATC	NO:
										AATGATTGC	752
										TTG[T/C]GCC
										AGTTCATGA
										TCATTGCTCT
										CAAAAGCAT
										GTGCAGCAG
chr	178139	C	T	ZNF35	p.E498	0.020	0.002	8.40	8.69	GATTACTAA	SEQ
5	385			4A	E	34	38	E-	[6.78-	GTGATGAGT	ID
								44	11.1	TACACCTGA	NO:
									4]	ATGTTTTCCC	753
										ACA[C/T]TCG
										TTACATTTAT
										AGGGTCTTT
										CTCCAGTAT
										GCATTCTCT
chr	178139	T	C	ZNF35	p.K49	0.020	0.002	4.38	7.3[5	GTGATGAGT	SEQ
5	394			4A	5K	34	84	E-	.72-	TACACCTGA	ID
								39	9.32]	ATGTTTTCCC	NO:
										ACACTCGTT	754
										ACA[T/C]TTA
										TAGGGTCTT
										TCTCCAGTA
										TGCATTCTCT
										GATGTTGAA
chr	179192	A	G	MAML1	p.T110	0.010	0.007	4.35	1.4[1	AAGTCATTC	SEQ
5	341				T	54	57	E-	.03-	TTTTCAATGT	ID
								02	1.9]	TTTTCAGCAT	NO:
										CTTCATGAT	755
										AC[A/G]GTTA
										AGAGGAATC
										TTGACAGCG
										CCACTTCCC
										CTCAGAATG
chr	179192	C	T	MAML1	p.Y13	0.010	0.007	4.35	1.4[1	GCGCCACTT	SEQ
5	401				0Y	54	56	E-	.03-	CCCCTCAGA	ID
								02	1.9]	ATGGCGATC	NO:
										AACAGAATG	756
										GCTA[C/T]GG
										GGACCTCTT
										TCCTGGGCA
										TAAGAAGAC
										TCGCCGGGA
										GG
chr	117684	C	T	ADTR	p.T96	0.005	0.002	6.64	2.12	CACATTTCT	SEQ
6	82			P	T	53	61	E-	[1.22-	GTTAGATTA	ID
								03	3.46]	TGTACACAT	NO:
										CTTTGAAAC	757
										TTAC[C/T]GT
										GGATACAGG
										AAAAGCCAG
										AGTGGTGAA
										AAGCAGGTC
										TC
chr	260322	C	T	HIST1	p.K24	0.007	0.000	8.79	Inf	TTTTCACGCC	SEQ
6	17			H3B	K	11	00	E-		GCCGGTAGC	ID
								43		CGGCGCGCT	NO:
										CTTGCGAGC	758
										AGC[C/T]TTG
										GTAGCCAGC
										TGCTTGCGT
										GGCGCTTTA
										CCGCCGGTG
										G
chr	294087	T	G	OR10C1	p.M31	0.009	0.005	7.68	1.63	AAAGCTGCC	SEQ
6	21				0R	07	59	E-	[1.17-	CTAAAGAGA	ID
								03	2.27]	ACCATCCAG	NO:
										AAAACGGTG	759
										CCTA[T/G]GG
										AGATTTGAA
										AAGGGGGCG
										ATAGTGACT
										TCTGTGCAG
										TG
chr	300389	C	T	RNF39	p.L337	0.005	0.003	3.63	1.59	GTACAATGC	SEQ
6	42				L	88	72	E-	[1.04-	GGAGCGGAG	ID
								02	2.41]	CACGAGGGT	NO:
										CGCAGGTGC	760
										AGAA[C/T]AG
										CGGGAAGAT
										GCGCTCCCC
										CAGGGGGCC
										AGGCGCCTG
										GA
chr	306732	G	A	MDC1	p.A12	0.011	0.000	4.12	264.	AGGGGTCTT	SEQ
6	80				27V	76	04	E-	73[1	GACAGAGGA	ID
								64	05.3	TCTATTTTTT	NO:
									3-	CTTCCCCTA	761
									665.	GTA[G/A]CCT
									33]	GAGAGGTGG
										GTTCAGAGG
										TGACAGGTC
										GGTCGGTGG
										A
chr	309171	G	A	DPCR1	p.G29	0.020	0.000	2.77	Inf	GAGCTCACA	SEQ
6	10				0E	59	00	E-		CAATCTCTA	ID
								100		GCAGAGCCT	No:
										ACAGAACAT	762
										GGAG[G/A]A
										AGGACAGCC
										AATGAGAAC
										AACACACCA
										TCCCCAGCA
										GAG
chr	309174	T	C	DPCR1	p.T392	0.006	0.000	2.15	78.3	AGCCTACAG	SEQ
6	17				T	37	08	E-	3[27.	AACATGGAG	ID
								25	32-	AAAGGACAG	No:
									224.	CCAATGAGA	763
									54]	ACAC[T/C]AC
										ACCATCCCC
										AGCAGAGCC
										TACAGAACA
										TGGAGAAAG
										GA
chr	309178	A	G	DPCR1	p.E539	0.012	0.000	4.79	Inf	ACCCCACTG	SEQ
6	57				G	25	00	E-		GCCAATGAG	ID
								60		AACACCACA	No:
										CCATCCCCA	764
										GCAG[A/G]G
										CCTACAGAA
										AATAGAGAA
										AGGACAGCC
										AATGAGAAG
										ACC
chr	309181	G	A	DPCR1	p.G64	0.005	0.000	6.87	42.3	GAAAGGACA	SEQ
6	60				0E	64	13	E-	5[18.	GCCAATGAG	ID
								21	16-	AACACCACA	No:
									98.7	CCATCCCCA	765
									4]	GCAG[G/A]G
										CCTACAGAA
										AATAGAGAA
										ATGACAGCC
										AACGAGAAG
										ACC
chr	309207	A	C	DPCR1	p.Y13	0.005	0.002	4.32	1.75	GTTCTCATTC	SEQ
6	55				48S	21	99	E-	[0.98-	CTCCTTTCTC	ID
								02	2.88]	ATCCCAATC	No:
										ACAGGTCTC	766
										CT[A/C]TATG
										ATGCGGACA
										CGCCGCACA
										CTAACCCAG
										AACACCCAG
chr	309543	C	T	MUC21	p.S125	0.013	0.000	5.07	Inf	CAACCTCCA	SEQ
6	27				S	24	00	E-		GTGGGGCCA	ID
								73		GCACAGCCA	No:
										CCAACTCTG	767
										AGTC[C/T]AG
										CACACCCTC
										CAGTGGGGC
										CAGCACAGC
										CACCAACTC
										TG
chr	309544	A	G	MUC21	p.S163	0.019	0.000	1.38	Inf	AGCCACCAA	SEQ
6	39				G	61	00	E-		CTCTGACTC	ID
								116		CAGCACAAC	No:
										CTCCAGTGA	768
										GGCC[A/G]GC
										ACAGCCACC
										AACTCTGAG
										TCCAGCACA
										ACCTCCAGT
										GG
chr	309956	C	T	MUC22	p.S809	0.009	0.000	5.89	Inf	CTACAGTTT	SEQ
6	35				S	56	00	E-		CCACCACAG	ID
								43		GCTTGGAGA	No:
										CCACCACCA	769
										CTTC[C/T]AC
										TGAAGGCTC
										TGAGATGAC
										TACAGTCTC
										CACCACAGG
										TG
chr	316916	C	A	C6orf25	p.G10	0.005	0.002	2.87	2.08	TCCGGCGGC	SEQ
6	66				4G	39	60	E-	[1.35-	TGGAGCTCC	ID
								03	3.22]	TCTTGAGCG	No:
										CGGGGGACT	770
										CGGG[C/A]AC
										TTTTTTCTGC
										AAGGGCCGC
										CACGAGGAC
										GAGAGCCGT
										A
chr	317368	C	T	VWA7	p.R488	0.005	0.002	1.64	2.13	CAGGGCAGC	SEQ
6	35				Q	39	54	E-	[1.38-	CATGCTCTC	ID
								03	3.29]	CCCAACAAT	No:
										GGCTGCCAC	771
										GTCT[C/T]GA
										ATGTGCTGG
										TCTTTGGTG
										AAGATCACC
										TCTCCTCCTG
										A
chr	326342	A	G	HLA-	p.S35P	0.007	0.004	1.76	1.73	TGGCGGCTC	SEQ
6	82			DQB1		48	33	E-	[1.09-	TGGAGAGCA	ID
								02	2.64]	GCTGCCCTG	No:
										CACTTACCG	772
										GGAG[A/G]G
										TCTCTGCCCT
										CAGCCAGTA
										GGGAGCTCA
										GCATCGCCA
										GC
chr	327136	C	A	HLA-	p.P128	0.006	0.000	1.10	Inf	GTCACAGTG	SEQ
6	19			DQA2	H	62	00	E-		TTTTCCAAGT	ID
								39		TTCCTGTGA	No:
										CGCTGGGTC	773
										AGC[C/A]CAA
										CACCCTCAT
										CTGTCTTGTG
										GACAACATC
										TTTCCTCCT
chr	327140	T	G	HLA-	p.L219	0.020	0.000	4.06	2275	GCCTGAGAT	SEQ
6	58			DQA2	V	59	01	E-	.46[3	TCCAGCCCC	ID
								120	16.7	TATGTCAGA	NO:
									4-	GCTCACAGA	774
									1634	GACT[T/G]TG
									6.8]	GTCTGCGCC
										CTGGGGTTG
										TCTGTGGGC
										CTCATGGGC
										AT
chr	327141	C	G	HLA-	p.G23	0.012	0.000	1.19	Inf	CCCTGGGGT	SEQ
6	08			DQA2	5G	75	00	E-		TGTCTGTGG	ID
								75		GCCTCATGG	NO:
										GCATTGTGG	775
										TGGG[C/G]AC
										TGTCTTCATC
										ATCCAAGGC
										CTGCGTTCA
										GTTGGTGCT
										T
chr	327141	T	C	HLA-	p.T236	0.012	0.000	3.37	Inf	TGGGGTTGT	SEQ
6	11			DQA2	T	50	00	E-		CTGTGGGCC	ID
								74		TCATGGGCA	No:
										TTGTGGTGG	776
										GCAC[T/C]GT
										CTTCATCATC
										CAAGGCCTG
										CGTTCAGTT
										GGTGCTTCC
										A
chr	327141	C	G	HLA-	p.F238	0.016	0.000	4.00	Inf	TGTCTGTGG	SEQ
6	17			DQA2	L	91	00	E-		GCCTCATGG	ID
								100		GCATTGTGG	No:
										TGGGCACTG	777
										TCTT[C/G]AT
										CATCCAAGG
										CCTGCGTTC
										AGTTGGTGC
										TTCCAGACA
										CC
chr	328200	C	A	TAP1	p.V30	0.005	0.002	1.19	2.21	TGCACGTGG	SEQ
6	00				4L	39	45	E-	[1.43-	CCCATGGTG	ID
								03	3.42]	TTGTTATAG	NO:
										ATCCCGTCA	778
										CCCA[C/A]GA
										ACTCCAGCA
										CTGCACTAT
										AAAGAACCC
										GGAAAAAAA
										GG
chr	333658	G	T	KIFC1	p.R5S	0.005	0.003	3.11	1.62	CTCCTGGGT	SEQ
6	08					64	49	E-	[1.06-	ATTGTCTTA	ID
								02	2.47]	AGGGTCTCT	NO:
										TTTCCCAAC	779
										AGAG[G/T]TC
										CCCCCTATT
										GGAAGTAAA
										GGGGAACAT
										AGAACTGAA
										GA
chr	340039	C	T	GRM4	p.S520S	0.005	0.003	4.08	1.59	AGCTGATGC	SEQ
6	28					39	40	E-	[1.03-	TCATCCCTA	ID
								02	2.45]	GTCCCAGGA	No:
										AGATTCGGC	780
										GCAG[C/T]GA
										GCAGGTGCC
										AAGGTCGGG
										CTCAGCGAT
										CATGAGGAA
										GG
chr	357150	C	T	ARMC	p.I188I	0.005	0.002	1.08	1.84	AGGAACACT	SEQ
6	76			12		15	81	E-	[1.18-	CCATCAAAG	ID
								02	2.86]	TACTCGAAC	No:
										TGATCTCCA	781
										CCAT[C/T]TG
										GGACACGGA
										ACTGCACAT
										TGCGGGCCT
										CAGACTCCT
										CA
chr	367100	T	A	CPNE5	p.I593F	0.006	0.000	5.82	Inf	CCCAGGCCC	SEQ
6	50					62	00	E-		CAGCCACCT	ID
								39		GCCTGCTGA	No:
										GACCAGGTT	782
										CAGA[T/A]GT
										GCGTGTGCA
										GGGGGGACG
										CAGGGGGCG
										TGCGGGCTG
										GG
chr	392828	G	A	KCNK	p.Q25	0.007	0.004	4.28	1.75	CCTCAGCTT	SEQ
6	16			16	1X	84	49	E-	[1.23-	CCCAGTCCT	ID
								03	2.51]	TTCTTGGAT	No:
										ATGGGGAAG	783
										TCCT[G/A]GG
										GTGTGACTT
										GGACTCCTC
										TTGCTGCTGT
										AGAGCCTCT
										C
chr	441438	G	A	CAPN	p.A29	0.005	0.002	2.43	1.85	ACTGGAATC	SEQ
6	62			11	7T	21	82	E-	[1.04-	CATGACTGA	ID
								02	3.06]	CAAGATGCT	No:
										GGTGAGAGG	784
										GCAC[G/A]CT
										TACTCTGTG
										ACTGGCCTT
										CAGGATGTG
										AGTCCTGAG
										AA
chr	466559	C	G	TDRD6	p.A12A	0.012	0.000	4.48	Inf	TCAAGATGT	SEQ
6	01					01	00	E-		GCTCGACGC	ID
								58		CCGGAATGC	No:
										CGGCGCCGG	785
										GGGC[C/G]TC
										GCTGGCCCT
										GCGGGTGTC
										CTTCGTGGA
										CGTGCATCC
										CG
chr	560330	G	A	COL21A1	p.T343M	0.067	0.071	3.19	0.94	TACTAAGAG	SEQ
6	94					40	69	E-	[0.83-	ACGAATTTG	ID
								01	1.06]	GTGCCAGCC	NO:
										TTCATCAAA	786
										CAAC[G/A]TC
										TACAAAAAG
										AAAGTGTGG
										AAGATTCAT
										AAATAAAGC
										CC
chr	767318	G	A	IMPG1	p.N13	0.010	0.007	3.74	1.39	AACTCTAGG	SEQ
6	54				7N	78	76	E-	[1.03-	AACTTCTTA	ID
								02	1.89]	CTGTTGTAG	NO:
										GCATCTTGG	787
										TGTC[G/A]TT
										GAGTGTATT
										ATCGAGAAT
										TTCATTGAG
										GAGGGTGTC
										AT
chr	843032	T	C	SNAP91	p.T553	0.010	0.007	1.83	1.49	AAATTACCA	SEQ
6	30				A	78	26	E-	[1.09-	CCAAAGATA	ID
								02	2.04]	TCTAGAGCA	NO:
										GGAGGAGCA	788
										GTGG[T/C]GG
										CGGTGGCAG
										CGGAGGTGG
										TGGTAGTGG
										TGGTGGCAG
										CG
chr	854737	C	T	TBX18	p.G48	0.414	0.494	5.64	0.72	GCGCCGCCG	SEQ
6	58				R	71	51	E-	[0.68-	CCGCGGCTG	ID
								23	0.77]	CAGCCTCCG	NO:
										TCGTCCACG	789
										GCCC[C/T]CG
										CCGCCTCTTC
										GGCGCCCAG
										TTTTCGCCGC
										TTCTTCTGA
chr	861950	G	A	NT5E	p.V27	0.007	0.004	1.07	1.64	ATTCATAGT	SEQ
6	33				8I	60	66	E-	[1.14-	CACTTCTGA	ID
								02	2.35]	TGATGGGCG	NO:
										GAAGGTTCC	790
										TGTA[G/A]TC
										CAGGCCTAT
										GCTTTTGGC
										AAATACCTA
										GGCTATCTG
										AA
chr	905721	G	A	CASP8	p.G23	0.005	0.003	2.39	1.69	AATGGTGTT	SEQ
6	38			AP2	7D	39	19	E-	[1.1-	TGGTCACGT	ID
								02	2.61]	TCTCATTATC	NO:
										AGGTTGGCG	791
										AGG[G/A]TA
										GCTCAAATG
										AGGATAGTA
										GAAGAGGAA
										GAAAAGATA
										TT
chr	108882	A	T	FOXO3	p.S26C	0.005	0.000	2.37	20.8	TCCGCTCGA	SEQ
6	487					39	26	E-	1[10.	AGTGGAGCT	ID
								17	92-	GGACCCGGA	No:
									39.6	GTTCGAGCC	792
									5]	CCAG[A/T]GC
										CGTCCGCGA
										TCCTGTACG
										TGGCCCCTG
										CAAAGGCCG
										GA
chr	109867	T	C	AK9	p.E103	0.023	0.000	6.49	295.	CGTTCTCAG	SEQ
6	190				5E	28	08	E-	82[1	AATCTTCCTC	ID
								127	49.2	AAATTCAGG	No:
									3-	TCCCACTTTC	793
									586.	TT[T/C]TCAG
									43]	TTTTGAGTA
										GTAGTTTTTC
										TTGAAGAAC
										TTCTTCAA
chr	126073	T	G	HEY2	p.L74	0.005	0.003	3.66	1.58	GGGATCGGA	SEQ
6	212				L	88	72	E-	[1.05-	TAAATAACA	ID
								02	2.39]	GTTTATCTG	No:
										AGTTGAGAA	794
										GACT[T/G]GT
										GCCAACTGC
										TTTTGAAAA
										ACAAGTAAG
										CTATCCCCTC
										C
chr	136597	G	A	BCLA	p.P497	0.005	0.002	2.13	2.47	TCAAAGAGG	SEQ
6	174			F1	S	64	29	E-	[1.61-	TCTTTGAGCT	ID
								04	3.78]	TTTCAGACTT	No:
										TACCTGCTC	795
										AG[G/A]TGAC
										TGAGTTTCTT
										TCTTTACTGT
										TATTCTTTCA
										GAATTT
chr	136597	C	A	BCLA	p.E403	0.008	0.004	1.21	1.83	AGGACTGAC	SEQ
6	456			F1	X	58	71	E-	[1.3-	TTCCTGAAC	ID
								03	2.58]	TGTCTATAA	No:
										TCCTCTGTCT	796
										CCT[C/A]TGT
										GTCATCCCC
										TTCTGAATC
										ATTAAACTT
										TTGTTTTCCA
chr	137814	G	T	OLIG3	p.I124I	0.024	0.000	1.52	2806	TGAGCATGA	SEQ
6	936					51	01	E-	.41[3	GGATGTAGT	ID
								144	91.3	TTCTGGCGA	No:
									8-	GCAGGAGTG	797
									2012	TGGC[G/T]AT
									3.7]	CTTGGAGAG
										CTTGCGCAC
										CGACGGCCC
										ATGCGCGTA
										GG
chr	139113	A	T	CCDC	p.T271	0.008	0.002	7.18	3.81	ACAAAAACT	SEQ
6	926			28A	S	14	15	E-	[2.41-	CCATTTGGC	ID
								08	5.78]	AGATGCACA	NO:
										AGATGTTCC	798
										AAAT[A/T]CT
										TCTGCTAGC
										TAAAATGAA
										ATGTAGTTT
										GCTTTCTTGT
										G
chr	152457	C	T	SYNE1	p.E853	0.008	0.001	6.73	5.3[3	GGCACTGCA	SEQ
6	795				9E	36	60	E-	.21-	TCAGGGCAT	ID
								08	8.74]	CCTGCAGCA	NO:
										GGCCCCGCC	799
										ACTC[C/T]TC
										CAGCAGAGA
										GCACACTCG
										GTCCCAGCG
										CCCATTCAT
										CT
chr	155143	A	G	SCAF8	p.T629	0.005	0.003	3.35	1.59	TCAGAGCCC	SEQ
6	502				A	64	54	E-	[1.05-	AACTCCAGT	ID
								02	2.43]	TGAAAAGGA	NO:
										GACAGTGGT	800
										CACA[A/G]CC
										CAGGCAGAG
										GTTTTCCCTC
										CTCCTGTTGC
										TATGTTGCA
chr	158487	T	C	SYNE	p.M29	0.009	0.005	9.88	1.57	CAGTCCGAA	SEQ
6	551				7T	31	94	E-	[1.13-	TTCACAAAT	ID
								03	2.18]	TTCAAGCGG	NO:
										ATCCGGATT	801
										GCTA[T/C]GG
										GGACCTGGA
										ACGTGAACG
										GAGGAAAGC
										AGTTCCGGA
										GC
chr	167728	T	C	UNC9	p.Y38	0.007	0.000	1.30	7.62	CGTTCTGTTT	SEQ
6	725			3A	7H	35	97	E-	[5.08-	GAGAAGAGC	ID
								15	11.4	AAGGAAGCT	NO:
									41]	GCCTTCGCC	802
										AAT[T/C]ACC
										GCCTGTGGG
										AGGCCCTGG
										GCTTCGTCA
										TTGCCTTCG
										G
chr	331061	A	G	WI2-	p.K10	0.015	0.000	1.78	377.	GCGCGCAGG	SEQ
7				237311	3K	69	04	E-	58[5	TGCCGCGGT	ID
				.2				52	2.37-	CCGAGGGCC	NO:
									2722	ACGAGAAGG	803
									.42]	GCAA[A/G]G
										GCAACTACT
										GGACGTTCG
										CGGGCGGCT
										GCGAGTCGC
										TGC
chr	102700	G	A	CYP2	p.R328	0.023	0.000	9.98	1179	CCACCCTTT	SEQ
7	7			W1	H	77	02	E-	.78[2	GCCCCAGGC	ID
								133	90.7	CGGGTGCAG	NO:
									9-	GAGGAGCTA	804
									4786	GACC[G/A]CG
									.53]	TGCTGGGCC
										CTGGGCGGA
										CTCCCCGGC
										TGGAGGACC
										AG
chr	102837	C	T	CYP2	p.P464	0.010	0.007	2.76	1.43	CTGCAGAGG	SEQ
7	6			W1	L	78	56	E-	[1.05-	TACCGCCTG	ID
								02	1.94]	CTGCCCCCG	NO:
										CCTGGCGTC	805
										AGTC[C/T]GG
										CCTCCCTGG
										ACACCACGC
										CCGCCCGGG
										CTTTTACCAT
										G
chr	178430	C	T	ELEN1	p.R26	0.006	0.003	4.27	1.55	CGTGGCGGC	SEQ
7	8				C	13	97	E-	[1.02-	CGCCACCCT	ID
								02	2.34]	GCTGCACGC	NO:
										TGGCGGCCT	806
										GGCC[C/T]GC
										GCAGACTGC
										TGGCTGATC
										GAGGGCGAC
										AAGGGCTTC
										GT
chr	225589	C	G	MAD1	p.E236	0.007	0.004	1.35	1.62	CCAGCTCAG	SEQ
7	3			L1	D	35	54	E-	[1.12-	ACTTCATGTT	ID
								02	2.35]	CTTCACAAT	NO:
										CGCTGCATC	807
										CTG[C/G]TCT
										TGCAGGGAC
										AGCTTCTGC
										TCCAGATCC
										TGATGGAGG
										C
chr	418545	G	A	SDK1	p.P144	0.010	0.007	4.98	1.38	GCGCCACAG	SEQ
7	7				4P	05	28	E-	[1.01-	TGAGGCAGT	ID
								02	1.9]	TCACAGCCA	NO:
										CCGACCTGG	808
										CCCC[G/A]GA
										GTCCGCATA
										CATCTTCAG
										GCTGTCCGC
										CAAGACGAG
										GC
chr	485690	T	C	RADIL	p.Y56	0.009	0.006	2.59	1.47	GTGCACCTT	SEQ
7	4				5C	07	17	E-	[1.06-	GGAGACATA	ID
								02	2.06]	GTAGACGCA	NO:
										CTGCTGGAA	809
										GGCG[T/C]AC
										AGCACCACC
										TCCTCCAGC
										ACCGCCATG
										GCCTCCTCG
										CT
chr	602682	G	C	PAIS2	p.S523	0.006	0.003	1.88	1.66	CCTGAGAGT	SEQ
7	7				S	13	70	E-	[1.11-	CCACATGTT	ID
								02	2.49]	CCTGCGAGC	NO:
										CCCTGTCCC	810
										CTGG[G/C]GA
										GCTGGCCGC
										ATACTCGCT
										GCTGCAGTG
										ACTGCCCGT
										GT
chr	232218	A	G	NUPL2	p.Q36R	0.005	0.000	4.20	195.	CCCGGTGCT	SEQ
7	11					39	03	E-	45[5	AGGGGTGCA	ID
								29	8.48-	GGAGGAGGA	NO:
									653.	CGGCAGCAA	811
									28]	CCGC[A/G]GC
										AGCAGCCTT
										CAGGTGACT
										CTCCTCTGA
										ATCCTCCGC
										GG
chr	262176	A	G	NFE2L3	p.I233	0.001	not	4.03	Inf	GGAGAACTC	SEQ
7	89				V	47	found	E-		ACTTCAGCA	ID
								06		GAATGATGA	No:
										TGATGAAAA	812
										CAAA[A/G]TA
										GCAGAGAAA
										CCTGACTGG
										GAGGCAGAA
										AAGACCACT
										GA
chr	309219	G	T	FAM1	p.R696	0.006	0.000	2.24	370.	GCCTGCAGC	SEQ
7	12			88B	S	62	02	E-	83[8	CGGGGCTCC	ID
								37	8.15-	TGCGTGACT	No:
									1559	GGAGGACTG	813
									.92]	AGAG[G/T]CT
										CTTTGACTTG
										TACTACTAC
										GATGGCCTG
										GCCAACCAG
										C
chr	379885	G	T	EPDR1	p.G79	0.007	0.000	1.62	159.	CATTCCTCA	SEQ
7	90				W	11	04	E-	69[6	AAACTCCAC	ID
								37	1.78-	CTTTGAAGA	NO:
									412.	CCAGTACTC	814
									75]	CATC[G/T]GG
										GGGCCTCAG
										GAGCAGATC
										ACCGTCCAG
										GAGTGGTCG
										GA
chr	420072	T	C	GLI3	p.I808	0.006	0.002	4.10	2.47	CTGAGCAGA	SEQ
7	01				M	86	79	E-	[1.67-	TGCATGGTC	ID
								05	3.63]	TGATGTAGA	NO:
										ACTCACCAT	815
										TTCC[T/C]AT
										GAGAGGAGA
										GACCGCAGG
										GGCTTTAGG
										GGGTAGAAT
										GG
chr	441544	G	A	POLD2	p.C447C	0.006	0.004	4.50	1.53	CATCGTCCT	SEQ
7	53					13	02	E-	[1.02-	CTGCCCCGA	ID
								02	2.29]	AGCCCGAGA	NO:
										AGCTGATGG	816
										GCTG[G/A]CA
										GGCCAGGCT
										GCGCAGGTT
										CACAAGGCA
										GGCGGTCTG
										CG
chr	451239	C	T	NACA	p.K61	0.005	0.000	6.20	47.3	CTTCAGCCT	SEQ
7	25			D	8K	15	11	E-	7[17.	GCTGGGACA	ID
								19	85-	CAATCGTGG	NO:
									125.	CTGCAGCCA	817
									69]	CAGG[C/T]TT
										TGGGGCTGA
										TGAGAGATC
										TGTGTCTTGT
										AGGGGCAGA
										G
chr	479255	C	T	PKD1	p.R990	0.009	0.006	3.03	1.46	TGAAGTGGC	SEQ
7	20			L1	Q	56	56	E-	[1.06-	AGGTTGGCC	ID
								02	2.02]	AAGGGTCAC	NO:
										GGGTGAAGG	818
										TTCC[C/T]GT
										GAGAATGGT
										GTGGTCGTT
										GCATCAGGA
										TCTGCAGTG
										CC
chr	505717	C	A	DDC	p.M23	0.005	0.003	3.84	1.62	TGTCAAAGG	SEQ
7	55				9I	39	34	E-	[1.05-	AGCAGCATG	ID
								02	2.49]	TTGTGGTCC	NO:
										CCAGGGTGG	819
										CAAC[C/A]AT
										CTAGAGGGT
										AAAAAGCAG
										ACAGCCTTT
										TATTCCCCA
										GG
chr	506730	C	T	GRB10	p.P390	0.005	0.003	3.94	1.61	AGGCGTGGC	SEQ
7	32				P	39	37	E-	[1.04-	CCTCCTCCA	ID
								02	2.47]	GGGCTGCGC	NO:
										TCTGGGCCT	820
										CTGC[C/T]GG
										ATTCTCTATC
										ACGCGTCCT
										GTTTGCCCA
										GAAAAATCC
										A
chr	636803	C	A	ZNF73	p.G30	0.008	0.000	1.80	989.	TTCATACTG	SEQ
7	38			5P	3G	82	01	E-	53[1	GAGAGAGAC	ID
								51	35.6	CCTACAAAT	NO:
									4-	GTGAAGAAT	821
									7219	GTGG[C/A]AA
									.03]	AGCCTTTAG
										CGTATCCTC
										AGCCCTCAT
										TTACCACAA
										GA
chr	638092	C	A	ZNF736	p.I342I	0.014	0.000	8.84	Inf	GTAAACATA	SEQ
7	67					22	00	E-		AGAGAATTC	ID
								84		ATACTGGAG	NO:
										AGAAACCCT	822
										ACAT[C/A]TG
										TGAAGAATG
										TGGCAAAGC
										CTTTACCCG
										CTCCTCAAC
										CC
chr	871606	G	A	ABCB1	p.L884	0.007	0.005	4.73	1.46	CTCACCTTCC	SEQ
7	45				L	60	22	E-	[1.02-	CAGAACCTT	ID
								02	2.11]	CTAGTTCTTT	NO:
										CTTATCTTTC	823
										A[G/A]TGCTT
										GTCCAGACA
										ACATTTTCAT
										TTCAACAAC
										TCCTGCT
chr	889655	C	T	ZNF80	p.T108	0.006	0.003	1.55	1.98	TTCCCTGGT	SEQ
7	53			4B	61	62	35	E-	[1.34-	GCTTTTCCGT	ID
								03	2.93]	CTAATAAAT	NO:
										ATACTGGTG	824
										TGA[C/T]TGA
										TTCAACAGA
										GACCCAAGA
										AGACCAAAT
										AAATCTAGA
										C
chr	916030	C	T	AKAP9	p.S27L	0.005	0.002	6.73	1.92	TTTTCTTAGC	SEQ
7	56					39	82	E-	[1.24-	TTGCCCAGT	ID
								03	2.96]	TTCGACAAA	NO:
										GAAAAGCTC	825
										AGT[C/T]GGA
										TGGGCAGAG
										TCCTTCCAA
										GAAGCAGAA
										AAAAAAGAG
										A
chr	978223	G	A	LMTK2	p.A86	0.009	0.005	9.20	1.6[1	TGTCCCGGA	SEQ
7	61				2T	31	85	E-	.15-	GGACTGTCT	ID
								03	2.22]	CCACCAGGA	NO:
										CATCAGTCC	826
										AGAC[G/A]CT
										GTGACTGTC
										CCGGTTGAA
										ATTCTCTCA
										ACTGATGCC
										AG
chr	999995	T	C	ZCWP	p.R529	0.005	0.002	1.11	1.83	CCTGGCTGG	SEQ
7	51			W1	G	15	82	E-	[1.17-	TCAGAATCT	ID
								02	2.85]	GAATTCCCT	NO:
										TGGCCTTCTT	827
										TCC[T/C]TCC
										CATTCTGGG
										TGCAGGAGG
										AGCTGTGGA
										TTTCCTGCCT
chr	100228	G	T	TFR2	p.A37	0.006	0.004	2.67	1.58	ATAAGGGGA	SEQ
7	655				6D	62	19	E-	[1.07-	GCCTAGGAG	ID
								02	2.34]	GCTCCCCTG	No:
										CCATTCTTG	828
										GGGG[G/T]CC
										ACAGGGCCT
										TTGAGCTTC
										CTGGAGAGG
										AGGAAGGCA
										GA
chr	100633	G	A	MUC12	p.G32S	0.005	0.006	9.17	0.95	CTCTCAAAT	SEQ
7	938					88	17	E-	[0.63-	CACAGGCTC	ID
								01	1.44]	AACAGTAAA	No:
										CACCAGTAT	829
										TGGA[G/A]GT
										AATACAACT
										TCTGCATCC
										ACACCCAGT
										TCAAGCGAC
										CC
chr	100633	C	T	MUC12	p.T39I	0.000	0.000	1.85	7.1[0	GTAAACACC	SEQ
7	960					25	03	E-	.64-	AGTATTGGA	ID
								01	78.3	GGTAATACA	No:
									51]	ACTTCTGCA	830
										TCCA[C/T]AC
										CCAGTTCAA
										GCGACCCTT
										TTACCACCTT
										TAGTGACTA
										T
chr	100634	G	A	MUC12	p.A10	0.002	0.001	1.71	1.59	CCCAGGTGC	SEQ
7	145				1T	70	70	E-	[0.85-	AACTGGAAC	ID
								01	2.96]	AACACTCTT	No:
										CCCTTCCCA	831
										CTCT[G/A]CA
										ACCTCAGTT
										TTTGTTGGA
										GAACCTAAA
										ACCTCACCC
										AT
chr	100634	C	T	MUC12	p.T122I	0.000	0.000	1.84	7.15	CCTAAAACC	SEQ
7	209					25	03	E-	[0.65-	TCACCCATC	ID
								01	78.8	ACTTCAGCC	No:
									7]	TCAATGGAA	832
										ACAA[C/T]AG
										CGTTACCTG
										GCAGTACCA
										CAACAGCAG
										GCCTGAGTG
										AG
chr	100634	C	G	MUC12	p.P153	0.000	0.000	1.00	0.92	TTCTACAGT	SEQ
7	302				R	49	53	E+00	[0.22-	AGCCCCAGA	ID
									3.85]	TCACCAGAC	No:
										AGAACACTC	833
										TCAC[C/G]TG
										CCCGCACGA
										CAAGCTCAG
										GCGTCAGTG
										AAAAATCAA
										CC
chr	100634	C	T	MUC12	p.P172	0.006	0.006	7.62	1.06	CTCAGGCGT	SEQ
7	358				S	86	48	E-	[0.72-	CAGTGAAAA	ID
								01	1.56]	ATCAACCAC	NO:
										CTCCCACAG	834
										CCGA[C/T]CA
										GGCCCAACG
										CACACAATA
										GCGTTCCCT
										GACAGTACC
										AC
chr	100634	C	A	MUC12	p.T177	0.000	0.000	1.00	1.02	AAATCAACC	SEQ
7	374				K	25	24	E+00	[0.13-	ACCTCCCAC	ID
									7.75]	AGCCGACCA	NO:
										GGCCCAACG	835
										CACA[C/A]AA
										TAGCGTTCC
										CTGACAGTA
										CCACCATGC
										CAGGCGTCA
										GT
chr	100634	C	T	MUC12	p.P181	0.001	0.002	7.38	0.83	TCCCACAGC	SEQ
7	386				L	96	37	E-	[0.41-	CGACCAGGC	ID
								01	1.69]	CCAACGCAC	NO:
										ACAATAGCG	836
										TTCC[C/T]TG
										ACAGTACCA
										CCATGCCAG
										GCGTCAGTC
										AGGAATCTA
										CA
chr	100634	T	G	MUC12	p.I199	0.000	0.000	5.26	1.42	ATGCCAGGC	SEQ
7	440				S	25	17	E-	[0.18-	GTCAGTCAG	ID
								01	11.1	GAATCTACA	No:
									3]	GCTTCCCAC	837
										AGCA[T/G]CC
										CCGGCTCCA
										CAGACACAA
										CACTGTCCC
										CTGGCACTA
										CC
chr	100634	G	C	MUC12	p.D28	0.005	0.005	1.00	0.99	GGGAGAACC	SEQ
7	700				6H	39	46	E+00	[0.64-	TACCACCTT	ID
									1.52]	CCAGAGCTG	NO:
										GCCAAGCTC	838
										AAAG[G/C]A
										CACTTCGCC
										TGCACCTTCT
										GGTACCACA
										TCAGCCTTT
										GT
chr	100634	C	T	MUC12	p.T315	0.000	0.000	5.28	1.42	TCTACAACT	SEQ
7	788				I	25	17	E-	[0.18-	TATCACAGC	ID
								01	11.0	AGCCCGAGC	NO:
									7]	TCAACTCCA	839
										ACAA[C/T]CC
										ACTTTTCTGC
										CAGCTCCAC
										AACCTTGGG
										CCATAGTGA
										G
chr	100634	G	A	MUC12	p.R348	0.013	0.015	3.63	0.87	AGCAGCCCA	SEQ
7	887				H	97	95	E-	[0.67-	GTTGCAACT	ID
								01	1.14]	GCAACAACA	No:
										CCCCCACCT	840
										GCCC[G/A]CT
										CCGCGACCT
										CAGGCCATG
										TTGAAGAAT
										CTACAGCCT
										AC
chr	100635	A	T	MUC12	p.K39	0.000	0.000	6.69	1.3[0	GAAGAATCA	SEQ
7	034				71	49	38	E-	.31-	GCAACTTTC	ID
								01	5.53]	CACGGCAGC	No:
										ACAACACAC	841
										ACAA[A/T]AT
										CTTCAACTC
										CTAGCACCA
										CAGCTGCCC
										TAGCACATA
										CA
chr	100635	C	G	MUC12	p.T403	0.000	0.000	6.53	Inf	CACGGCAGC	SEQ
7	052				S	25	00	E-	[NaN-	ACAACACAC	ID
								02	Inf]	ACAAAATCT	No:
										TCAACTCCT	842
										AGCA[C/G]CA
										CAGCTGCCC
										TAGCACATA
										CAAGCTACC
										ACAGCAGCC
										TG
chr	100635	T	C	MUC12	p.L416	0.000	0.000	1.00	0.89	ACCACAGCT	SEQ
7	091				P	49	55	E+00	[0.21-	GCCCTAGCA	ID
									3.73]	CATACAAGC	No:
										TACCACAGC	843
										AGCC[T/C]GG
										GCTCAACTG
										AAACAACAC
										ACTTCCGTG
										ATAGCTCCA
										CA
chr	100635	C	G	MUC12	p.D46	0.000	0.001	6.61	0.7[0	TCTTACCTGC	SEQ
7	236				4E	98	41	E-	.26-	CGGCTCTAC	ID
								01	1.9]	ACCCTCAGT	No:
										TCTTGTTGG	844
										AGA[C/G]TCG
										ACGCCCTCA
										CCCATCAGT
										TCAGGCTCA
										ATGGAAACC
										A
chr	100635	C	A	MUC12	p.P469	0.001	0.001	6.90	0.71	TCTACACCC	SEQ
7	250				H	23	72	E-	[0.29-	TCAGTTCTTG	ID
								01	1.75]	TTGGAGACT	No:
										CGACGCCCT	845
										CAC[C/A]CAT
										CAGTTCAGG
										CTCAATGGA
										AACCACAGC
										GTTACCCGG
										C
chr	100635	A	C	MUC12	p.M47	0.000	0.000	3.33	2.86	TGTTGGAGA	SEQ
7	267				5L	25	09	E-	[0.33-	CTCGACGCC	ID
								01	24.4	CTCACCCAT	No:
									9]	CAGTTCAGG	846
										CTCA[A/C]TG
										GAAACCACA
										GCGTTACCC
										GGCAGTACC
										ACAAAACCA
										GG
chr	100635	A	G	MUC12	p.S498	0.005	0.005	8.30	1.03	CACAAAACC	SEQ
7	336				G	88	70	E-	[0.68-	AGGCCTCAG	ID
								01	1.56]	TGAGAAATC	No:
										TACCACTTTC	847
										TAC[A/G]GTA
										GCCCCAGAT
										CACCAGACA
										CAACACACT
										TACCTGCCA
										G
chr	100635	C	G	MUC12	p.H52	0.000	0.000	4.92	1.59	TGACAAGCT	SEQ
7	419				5Q	25	15	E-	[0.2-	CAGGCGTCA	ID
								01	12.5	GTGAAGAAT	No:
									4]	CCACCACCT	848
										CCCA[C/G]AG
										CCGACCAGG
										CTCAACACA
										CACAACAGC
										ATTCCCTGG
										CA
chr	100635	C	A	MUC12	p.T533	0.000	0.000	1.26	14.3	GAATCCACC	SEQ
7	442				K	25	02	E-	2[0.9-	ACCTCCCAC	ID
								01	228.	AGCCGACCA	No:
									9]	GGCTCAACA	849
										CACA[C/A]AA
										CAGCATTCC
										CTGGCAGTA
										CCACCATGC
										CAGGCCTCA
										GT
chr	100635	C	G	MUC12	p.L602	0.000	0.000	1.00	0.71	AACAACACT	SEQ
7	648				V	49	69	E+00	[0.17-	CTTACCTGA	ID
									2.95]	CAACACCAC	No:
										AGCCTCAGG	850
										ACTC[C/G]TT
										GAAGCATCT
										ATGCCCGTC
										CACAGCAGC
										ACCAGATCG
										CC
chr	100635	A	C	MUC12	p.E603	0.001	0.000	1.73	1.75	ACACTCTTA	SEQ
7	652				A	47	84	E-	[0.75-	CCTGACAAC	ID
								01	4.09]	ACCACAGCC	No:
										TCAGGACTC	851
										CTTG[A/C]AG
										CATCTATGC
										CCGTCCACA
										GCAGCACCA
										GATCGCCAC
										AC
chr	100635	G	A	MUC12	p.S614	0.005	0.003	3.40	1.68	TCCTTGAAG	SEQ
7	686				S	39	22	E-	[1.08-	CATCTATGC	ID
								02	2.61]	CCGTCCACA	No:
										GCAGCACCA	852
										GATC[G/A]CC
										ACACACAAC
										ACTGTCCCC
										TGCCGGCTC
										TACAACCCG
										TC
chr	100635	C	T	MUC12	p.P657	0.004	0.003	7.98	1.04	AGGCCTGCA	SEQ
7	814				L	17	99	E-	[0.64-	CCTCCTACT	ID
								01	1.71]	ACCACATCA	No:
										GCCTTTGTTG	853
										AGC[C/T]ATC
										TACAACCTC
										CCACGGCAG
										CCCGAGCTC
										AATTCCAAC
										A
chr	100635	C	G	MUC12	p.H67	0.000	0.000	4.91	1.59	TACAACCTC	SEQ
7	858				2D	25	15	E-	[0.2-	CCACGGCAG	ID
								01	12.5	CCCGAGCTC	No:
									5]	AATTCCAAC	854
										AACC[C/G]AC
										ATTTCTGCCC
										GCTCCACAA
										CCTCAGGCC
										TCGTTGAAG
										A
chr	100635	T	A	MUC12	p.S674	0.000	0.000	7.03	3.58	CTCCCACGG	SEQ
7	864				T	74	21	E-	[1.01-	CAGCCCGAG	ID
								02	12.6	CTCAATTCC	No:
									9]	AACAACCCA	855
										CATT[T/A]CT
										GCCCGCTCC
										ACAACCTCA
										GGCCTCGTT
										GAAGAATCT
										AC
chr	100635	G	A	MUC12	p.R676	0.000	0.000	1.84	7.15	GGCAGCCCG	SEQ
7	871				H	25	03	E-	[0.65-	AGCTCAATT	ID
								01	78.8	CCAACAACC	No:
									7]	CACATTTCT	856
										GCCC[G/A]CT
										CCACAACCT
										CAGGCCTCG
										TTGAAGAAT
										CTACGACCT
										AC
chr	100635	C	A	MUC12	p.T679	0.004	0.003	2.87	1.28	AGCTCAATT	SEQ
7	880				N	66	65	E-	[0.8-	CCAACAACC	ID
								01	2.04]	CACATTTCT	No:
										GCCCGCTCC	857
										ACAA[C/A]CT
										CAGGCCTCG
										TTGAAGAAT
										CTACGACCT
										ACCACAGCA
										GC
chr	100635	C	G	MUC12	p.S695	0.000	0.000	3.71	Inf	CTCGTTGAA	SEQ
7	928				X	25	00	E-	[NaN-	GAATCTACG	ID
								02	Inf]	ACCTACCAC	No:
										AGCAGCCCG	858
										GGCT[C/G]AA
										CTCAAACAA
										TGCACTTCC
										CTGAAAGCG
										ACACAACTT
										CA
chr	100636	C	A	MUC12	p.S910	0.005	0.016	8.63	0.35	AGCACCACC	SEQ
7	573				Y	64	13	E-	[0.23-	ACCTCAGGC	ID
								09	0.53]	CCCAGTCAG	No:
										GAATCAACA	859
										ACTT[C/A]CC
										ACAGCAGCT
										CAGGTTCAA
										CTGACACAG
										CACTGTCCC
										CT
chr	100636	G	A	MUC12	p.R974	0.000	0.000	2.64	18.6	GAAGCATCT	SEQ
7	765				H	49	03	E-	3[1.6	ACACGCGTC	ID
								02	9-	CACAGCAGC	No:
									205.	ACTGGCTCA	860
									52]	CCAC[G/A]CA
										CAACACTGT
										CCCCTGCCA
										GCTCCACAA
										GCCCTGGAC
										TT
chr	100636	C	G	MUC12	p.T996	0.000	0.000	2.81	2.12	ACAAGCCCT	SEQ
7	831				S	49	23	E-	[0.46-	GGACTTCAG	ID
								01	9.8]	GGAGAATCT	No:
										ACTGCCTTC	861
										CAGA[C/G]CC
										ACCCAGCCT
										CAACTCACA
										CAACGCCTT
										CACCTCCTA
										GC
chr	100636	T	C	MUC12	p.S100	0.005	0.006	3.48	0.78	TGCCTTCCA	SEQ
7	860				6P	15	58	E-	[0.5-	GACCCACCC	ID
								01	1.22]	AGCCTCAAC	No:
										TCACACAAC	862
										GCCT[T/C]CA
										CCTCCTAGC
										ACCGCAACA
										GCCCCTGTT
										GAAGAATCT
										AC
chr	100637	C	G	MUC12	p.P113	0.006	0.000	5.46	250.	CTGGGCGTC	SEQ
7	251				6R	37	03	E-	3[33.	GGTGAAGAA	ID
								26	96-	TCCACCACC	No:
									1844	TCCCGTAGC	863
									.95]	CAAC[C/G]AG
										GTTCTACTC
										ACTCAACAG
										TGTCACCTG
										CCAGCACCA
										CC
chr	100637	C	G	MUC12	p.T118	0.001	0.001	4.55	1.37	CACAGCACC	SEQ
7	407				8S	47	07	E-	[0.58-	ACAACCTCA	ID
								01	3.23]	GTTCATGGT	No:
										GAAGAGCCT	864
										ACAA[C/G]CT
										TCCACAGCC
										GGCCAGCCT
										CAACTCACA
										CAACACTGT
										TC
chr	100637	G	A	MUC12	p.G12	0.008	0.011	1.98	0.79	CCAAACAGG	SEQ
7	556				38S	82	19	E-	[0.56-	GTTACCTGC	ID
								01	1.11]	CACACTCAC	No:
										AACCGCAGA	865
										CCTC[G/A]GT
										GAGGAATCA
										ACTACCTTTC
										CCAGCAGCT
										CAGGCTCAA
										C
chr	100637	C	T	MUC12	p.P135	0.001	0.001	1.00	0.87	TTCCCTGAC	SEQ
7	902				3L	47	69	E+0	[0.37-	AGCACCACC	ID
								0	2.04]	ACCTCAGAC	No:
										CTCAGTCAG	866
										GAAC[C/T]TA
										CAACTTCCC
										ACAGCAGCC
										AAGGCTCAA
										CAGAGGCAA
										CA
chr	100638	C	G	MUC12	p.H15	0.006	0.000	1.36	Inf	CGACAAGCT	SEQ
7	584				80Q	13	00	E-		CAGGCGTCA	ID
								29		GTGAAGAAT	No:
										CCACCACCT	867
										CCCA[C/G]AG
										CCGACCAGG
										CTCAACGCA
										CACAACAGC
										ATTCCCTGG
										CA
chr	100638	G	T	MUC12	p.S161	0.001	0.000	1.36	21.2	ATGCCAGGC	SEQ
7	673				0I	47	07	E-	8[6-	GTCAGTCAG	ID
								05	75.4	GAATCTACA	No:
									4]	GCTTCCCAC	868
										AGCA[G/T]CC
										CAGGCTCCA
										CAGACACAA
										CATTGTCCC
										CTGGCAGTA
										CC
chr	100638	G	A	MUC12	p.S163	0.000	0.000	2.36	14.2	ACAGCATCA	SEQ
7	754				7N	49	03	E-	5[2.0	TCCCTTGGTC	ID
								02	1-	CAGAATCTA	No:
									101.	CTACTTTCCA	869
									22]	CA[G/A]CAGC
										CCAGGCTCC
										ACTGAAACA
										ACACTCTTA
										CCTGACAAC
chr	100638	C	T	MUC12	p.S166	0.000	0.000	6.13	1.1[0	CTCCTTGAA	SEQ
7	850				9L	25	22	E-	.14-	GCATCTACG	ID
								01	8.39]	CCCGTCCAC	No:
										AGCAGCACT	870
										GGAT[C/T]GC
										CACACACAA
										CACTGTCCC
										CTGCCGGCT
										CTACAACAC
										GT
chr	100638	G	A	MUC12	p.R168	0.001	0.000	2.33	1.7[0	TCGCCACAC	SEQ
7	889				2H	23	72	E-	.67-	ACAACACTG	ID
								01	4.31]	TCCCCTGCC	No:
										GGCTCTACA	871
										ACAC[G/A]TC
										AGGGAGAAT
										CTACCACCT
										TCCAGAGCT
										GGCCAAGCT
										CA
chr	100638	G	A	MUC12	p.W16	0.000	0.000	1.84	7.15	TCTACAACA	SEQ
7	919				92X	25	03	E-	[0.65-	CGTCAGGGA	ID
								01	78.9]	GAATCTACC	No:
										ACCTTCCAG	872
										AGCT[G/A]GC
										CAAGCTCAA
										AGGACACTA
										TGCCTGCAC
										CTCCTACTA
										CC
chr	100638	C	G	MUC12	p.P169	0.000	0.000	6.53	Inf	ACAACACGT	SEQ
7	922				3R	25	00	E-	[NaN-	CAGGGAGAA	ID
								02	Inf]	TCTACCACC	No:
										TTCCAGAGC	873
										TGGC[C/G]AA
										GCTCAAAGG
										ACACTATGC
										CTGCACCTC
										CTACTACCA
										CA
chr	100638	G	A	MUC12	p.S169	0.000	0.000	6.45	1.51	ACACGTCAG	SEQ
7	925				4N	49	33	E-	[0.35-	GGAGAATCT	ID
								01	6.47][	ACCACCTTC	No:
										CAGAGCTGG	874
										CCAA[G/A]CT
										CAAAGGACA
										CTATGCCTG
										CACCTCCTA
										CTACCACAT
										CA
chr	100638	C	G	MUC12	p.S169	0.000	0.000	3.71	Inf	CGTCAGGGA	SEQ
7	928				5X	25	00	E-	[NaN-	GAATCTACC	ID
								02	Inf][	ACCTTCCAG	No:
										AGCTGGCCA	875
										AGCT[C/G]AA
										AGGACACTA
										TGCCTGCAC
										CTCCTACTA
										CCACATCAG
										CC
chr	100643	C	G	MUC12	p.H31	0.017	0.000	9.03	Inf	CGACAAGCT	SEQ
7	255				37Q	16	00	E-		CAGGCGTCA	ID
								84		GTGAAGAAT	No:
										CCACCACCT	876
										CCCA[C/G]AG
										CCGACCAGG
										CTCAACGCA
										CACAACAGC
										ATTCCCTGG
										CA
chr	100643	G	A	MUC12	p.A31	0.005	0.001	2.43	3.89	AGGCTCCAC	SEQ
7	388				82T	88	52	E-	[2.47-	AGACACAAC	ID
								07	6.12][	ACTGTCCCC	No:
										TGGCAGTAC	877
										CACA[G/A]CA
										TCATCCCTTG
										GTCCAGAAT
										CTACTACCTT
										CCACAGCGG
chr	100643	G	A	MUC12	p.R323	0.003	0.000	2.27	44.8	TCGCCACAC	SEQ
7	560				9H	92	09	E-	5[16.	ACAACACTG	ID
								15	42-	TCCCCTGCC	No:
									122.	GGCTCTACA	878
									48]	ACCC[G/A]TC
										AGGGAGAAT
										CTACCACCT
										TCCAGAGCT
										GGCCTAACT
										CG
chr	100643	A	G	MUC12	p.T324	0.000	0.000	3.74	9.54	ACTGTCCCC	SEQ
7	574				4A	49	05	E-	[1.59-	TGCCGGCTC	ID
								02	57.1	TACAACCCG	No:
									3]	TCAGGGAGA	879
										ATCT[A/G]CC
										ACCTTCCAG
										AGCTGGCCT
										AACTCGAAG
										GACACTACC
										CC
chr	100643	C	T	MUC12	p.S329	0.000	0.000	6.47	1.48	TTTTCTGCCA	SEQ
7	737				8L	49	33	E-	[0.34-	GCTCCACAA	ID
								01	6.34]	CCTTGGGCC	No:
										GTAGTGAGG	880
										AAT[C/T]GAC
										AACAGTCCA
										CAGCAGCCC
										AGTTGCAAC
										TGCAACAAC
										A
chr	100643	G	A	MUC12	p.R331	0.008	0.000	1.03	36.5	AGCAGCCCA	SEQ
7	791				6H	09	22	E-	9[18.	GTTGCAACT	ID
								28	88-	GCAACAACA	No:
									70.9]	CCCTCGCCT	881
										GCCC[G/A]CT
										CCACAACCT
										CAGGCCTCG
										TTGAAGAAT
										CTACGACCT
										AC
chr	100646	G	A	MUC12	p.S424	0.000	0.000	4.92	1.36	ACCATGCCA	SEQ
7	590				9N	74	54	E-	[0.42-	GGCGTCAGT	ID
								01	4.44]	CAGGAATCT	NO:
										ACAGCTTCC	882
										CACA[G/A]CA
										GCCCAGGCT
										CCACAGACA
										CAACACTGT
										CCCCTGGCA
										GT
chr	100646	A	C	MUC12	p.N42	0.021	0.051	5.47	0.4[0	CAGCAGCCC	SEQ
7	712				90H	08	65	E-	.32-	AGGCTCCAC	ID
								22	0.49]	TGAAACAAC	NO:
										ACTCTTACCT	883
										GAC[A/C]ACA
										CCACAGCCT
										CAGGCCTCC
										TTGAAGCAT
										CTACACCCG
										T
chr	100646	C	G	MUC12	p.P430	0.022	0.000	6.14	313.	GACAACACC	SEQ
7	749				2R	55	07	E-	86[9	ACAGCCTCA	ID
								92	9.34-	GGCCTCCTT	NO:
									991.	GAAGCATCT	884
									56]	ACAC[C/G]CG
										TCCACAGCA
										GCACTGGAT
										CGCCACACA
										CAACACTGT
										CC
chr	100646	G	A	MUC12	p.R432	0.000	0.000	1.00	0.89	TCGCCACAC	SEQ
7	809				2H	25	27	E+00	[0.12-	ACAACACTG	ID
									6.73]	TCCCCTGCC	NO:
										GGCTCTACA	885
										ACCC[G/A]TC
										AGGGAGAAT
										CTACCACCT
										TCCAGAGCT
										GGCCAAACT
										CG
chr	100646	C	T	MUC12	p.R437	0.002	0.002	8.75	0.89	TCCAACAAC	SEQ
7	973				7C	45	75	E-	[0.47-	CCACTTTTCT	ID
								01	1.7]	GCCAGCTCC	NO:
										ACAACATTG	886
										GGC[C/T]GTA
										GTGAGGAAT
										CGACAACAG
										TCCACAGCA
										GCCCAGTTG
										C
chr	100647	A	G	MUC12	p.R463	0.000	0.000	6.60	Inf	CCCTGAAAG	SEQ
7	735				1G	25	00	E-	[NaN-	CTCCACAGC	ID
								02	Inf]	TTCAGGTCG	NO:
										TAGTGAAGA	887
										ATCA[A/G]GA
										ACTTCCCAC
										AGCAGCACA
										ACACACACA
										ATATCTTCA
										CC
chr	100647	C	G	MUC12	p.P464	0.006	0.006	9.21	0.95	AAGAACTTC	SEQ
7	774				4A	37	73	E-	[0.64-	CCACAGCAG	ID
								01	1.41]	CACAACACA	No:
										CACAATATC	888
										TTCA[C/G]CT
										CCTAGCACC
										ACATCTGCC
										CTTGTTGAA
										GAACCTACC
										AG
chr	100647	C	G	MUC12	p.S471	0.005	0.003	1.60	1.37	TTACCTGCC	SEQ
7	976				1C	39	95	E-	[0.88-	CATTTTACTA	ID
								01	2.12]	CCTCAGGCC	No:
										GCATTGCAG	889
										AAT[C/G]TAC
										CACCTTCTAT
										ATCTCTCCA
										GGCTCAATG
										GAAACAACA
chr	100647	A	G	MUC12	p.Y47	0.000	0.000	2.36	14.2	TTTACTACCT	SEQ
7	988				15C	49	03	E-	7[2.0	CAGGCCGCA	ID
								02	1-	TTGCAGAAT	No:
									101.	CTACCACCT	890
									32]	TCT[A/G]TAT
										CTCTCCAGG
										CTCAATGGA
										AACAACATT
										AGCCAGCAC
										T
chr	100648	C	G	MUC12	p.L473	0.005	0.006	7.56	0.91	AATGGAAAC	SEQ
7	044				4V	64	19	E-	[0.6-	AACATTAGC	ID
								01	1.39]	CAGCACTGC	No:
										CACAACACC	891
										AGGC[C/G]TC
										AGTGCAAAA
										TCTACCATC
										CTTTACAGT
										AGCTCCAGA
										TC
chr	100648	C	G	MUC12	p.S476	0.000	0.000	3.78	2.38	CCAGCATGA	SEQ
7	148				8R	25	10	E-	[0.29-	CAAGCTCCA	ID
								01	19.7	GCATCAGTG	No:
									51]	GAGAACCCA	892
										CCAG[C/G]TT
										GTATAGCCA
										AGCAGAGTC
										AACACACAC
										AACAGCGTT
										CC
chr	100648	C	T	MUC12	p.A47	0.000	0.000	1.84	7.12	ACCAGCTTG	SEQ
7	183				80V	25	03	E-	[0.65-	TATAGCCAA	ID
								01	78.5	GCAGAGTCA	No:
									51]	ACACACACA	893
										ACAG[C/T]GT
										TCCCTGCCA
										GCACCACCA
										CCTCAGGCC
										TCAGTCAGG
										AA
chr	100649	G	T	MUC12	p.C498	0.000	0.000	7.00	1.12	CACGGTGAC	SEQ
7	758				8F	49	44	E-	[0.27-	TGCTGTGGA	ID
								01	4.73]	TTCTATCTCT	No:
										CCACAGGGT	894
										TGT[G/T]CCA
										GGAAGGACA
										AATTTGGAA
										TGGAAAACA
										ATGCGTCTG
										T
chr	100649	G	C	MUC12	p.G50	0.000	0.000	2.41	4.67	TGGAATGGA	SEQ
7	815				07A	25	05	E-	[0.49-	AAACAATGC	ID
								01	44.9	GTCTGTCCC	No:
									4]	CAAGGCTAC	895
										GTTG[G/C]TT
										ACCAGTGCT
										TGTCCCCTCT
										GGAATCCTT
										CCCTGTAGG
										T
chr	100649	C	T	MUC12	p.P501	0.000	0.000	2.59	0.29	CTACGTTGG	SEQ
7	847				8S	25	86	E-	[0.04-	TTACCAGTG	ID
								01	2.07]	CTTGTCCCCT	No:
										CTGGAATCC	896
										TTC[C/T]CTG
										TAGGTAATG
										ACCTTTTCTG
										AGACCTGCA
										GCTCTTTGC
chr	100649	T	C	MUC12	p.V50	0.000	0.000	9.98	3[0.8	GTTGGTTAC	SEQ
7	851				19A	74	24	E-	6-	CAGTGCTTG	ID
								02	10.4	TCCCCTCTG	No:
									6]	GAATCCTTC	897
										CCTG[T/C]AG
										GTAATGACC
										TTTTCTGAG
										ACCTGCAGC
										TCTTTGCAG
										GC
chr	100651	C	T	MUC12	p.P502	0.000	0.000	4.29	1.69	GCTGTCTCA	SEQ
7	921				2L	74	43	E-	0[.51-	CGCATACCA	ID
								01	5.6]	TGGCCTTTTC	No:
										CCACAGAAA	898
										CCC[C/T]GGA
										AAAACTCAA
										CGCCACTTT
										AGGTATGAC
										AGTGAAAGT
										G
chr	100656	T	C	MUC12	p.L520	0.000	0.000	1.29	14.0	AAGTGCACC	SEQ
7	384				0P	25	02	E-	2[0.8	AAAGGAACG	ID
								01	8-	AAGTCGCAA	No:
									224.	ATGAACTGT	899
									21]	AACC[T/C]GG
										GCACATGTC
										AGCTGCAAC
										GCAGTGGCC
										CCCGCTGCC
										TG
chr	100657	T	C	MUC12	p.I523	0.000	0.000	6.19	1.08	AACACACAC	SEQ
7	247				1T	25	23	E-	[0.14-	TGGTACTGG	ID
								01	8.25]	GGAGAGACC	NO:
										TGTGAATTC	900
										AACA[T/C]CG
										CCAAGAGCC
										TCGTGTATG
										GGATCGTGG
										GGGCTGTGA
										TG
chr	100678	G	A	MUC17	p.P140	0.018	0.000	2.01	1009	GAACCACTC	SEQ
7	918				7P	14	02	E-	.33[2	CGTTAACAA	ID
								104	47.6	GTATACCTG	NO:
									9-	TCAGCACCA	901
									4112	CGCC[G/A]GT
									.96]	AGTCAGTTC
										TGAGGCTAG
										CACCCTTTC
										AGCAACTCC
										TG
chr	100681	C	T	MUC17	p.A21	0.012	0.000	8.18	Inf	CTCCTTTAAC	SEQ
7	219				74A	99	00	E-		AAGTATGCC	ID
								78		TGTCAGCAC	No:
										CACAGTGGT	902
										GGC[C/T]AGT
										TCTGCAATC
										AGCACCCTT
										TCAACAACT
										CCTGTTGAC
										A
chr	100681	T	G	MUC17	p.S220	0.0006	0.000	2.25	Inf	TGTGACCAA	SEQ
7	310				5A	37	00	E-		TTCTACTGA	ID
								38		AGCCCGTTC	NO:
										ATCTCCTAC	903
										AACT[T/G]CT
										GAAGGTACC
										AGCATGCCA
										ACCTCAACT
										CCTAGTGAA
										GG
chr	100682	T	C	MUC17	p.S263	0.007	0.001	4.22	4.95	TACCAGCAT	SEQ
7	597				4P	11	44	E-	[3.33-	GCCAATCTC	ID
								11	7.38]	AACTCCTAG	NO:
										TGAAGTAAG	904
										TACT[T/C]CA
										TTAACAAGT
										ATACTTGTC
										AGCACCATG
										CCAGTGGCC
										AG
chr	100682	T	C	MUC17	p.L263	0.006	0.000	2.08	14.3	TCAACTCCT	SEQ
7	613				9P	86	48	E-	2[9.0	AGTGAAGTA	ID
								20	5-	AGTACTTCA	NO:
									22.6	TTAACAAGT	905
									5]	ATAC[T/C]TG
										TCAGCACCA
										TGCCAGTGG
										CCAGTTCTG
										AGGCTAGCA
										CC
chr	102087	C	T	ORAI2	p.L168	0.011	0.006	2.80	1.82	TGCTTGGCA	SEQ
7	238				L	27	23	E-	[1.35-	TCCTACTCTT	ID
								04	2.46]	CCTGGCCGA	No:
										GGTGGTGCT	906
										GCT[C/T]TGC
										TGGATCAAG
										TTCCTCCCCG
										TGGATGCCC
										GGCGCCAGC
chr	108112	A	G	PNPL	p.D76	0.005	0.003	1.58	1.69	ATGGAAGTC	SEQ
7	902			A8	4D	88	48	E-	[1.12-	CTTCATACA	ID
								02	2.56]	TATCAGTTTT	No:
										TAATTTTATC	907
										CA[A/G]TCAT
										TAATTTTCTG
										CAGAGTTGT
										TTTTTCTTGA
										CTTAATA
chr	111368	G	A	DOCK4	p.P191	0.009	0.005	2.33	1.74	CGCGGGCGG	SEQ
7	481				7L	31	38	E-	[1.25-	CTCCGACGT	ID
								03	2.42]	GACGGGGAT	No:
										GGAGAGGCT	908
										GTGA[G/A]GT
										AGCGGGACG
										GGGCGCCGC
										AGAGTCCGC
										TCGTAGACG
										CT
chr	117232	A	G	CFTR	p.E695	0.021	0.000	3.53	2406	ACAAAAAAA	SEQ
7	305				G	32	01	E-	.22[3	CAATCTTTTA	ID
								125	35.0	AACAGACTG	No:
									8-	GAGAGTTTG	909
									1727	GGG[A/G]AA
									9.21]	AAAGGAAGA
										ATTCTATTCT
										CAATCCAAT
										CAACTCTAT
										A
chr	123143	G	A	IQUB	p.P278	0.007	0.004	1.12	1.65	ACATTACCT	SEQ
7	031				P	84	78	E-	[1.15-	GCGTATCCC	ID
								02	2.36]	TACAAAATA	No:
										TACTGAGTC	910
										TTTC[G/A]GG
										AATCCTTTTA
										GGTACAGTT
										TGTGTTCCA
										GCATTGTGA
										T
chr	141366	A	G	KIAA1	p.M23	0.006	0.004	4.89	1.52	GATGAGGAT	SEQ
7	203			147	5T	37	20	E-	[1.02-	CTGTTCTCCA	ID
								02	2.26]	AAGAACTTT	No:
										ATAAACTGA	911
										GAC[A/G]TGC
										AGCCAGCTG
										GGTGTGTGA
										TCTGAAAAA
										ATTGAGGGG
										A
chr	141763	C	A	MGAM	p.P142	0.012	0.009	2.68	1.38	GAGGTATGT	SEQ
7	311				4T	99	45	E-	[1.05-	CTGTGTTTG	ID
								02	1.82]	GCATTTCTA	No:
										GGATATGAA	912
										TGAA[C/A]CA
										TCAAGCTTC
										GTGAATGGG
										GCAGTTTCT
										CCAGGCTGC
										AG
chr	141794	C	T	MGAM	p.F154	0.006	0.002	1.83	2.75	CTGTGCTTCT	SEQ
7	442				7F	13	24	E-	[1.82-	CGTTGCAGG	ID
								05	4.15]	CATGATGGA	No:
										GTTCAGCCT	913
										CTT[C/T]GGC
										ATATCCTAT
										GTGAGTGTC
										CTTGGGATC
										CTCCTAAGC
										A
chr	150069	G	A	REPIN1	p.K24	0.009	0.000	1.71	Inf	CCTTCCAGT	SEQ
7	074				8K	56	00	E-		GTGCCTGTT	ID
								56		GTGGCAAGC	No:
										GCTTCCGGC	914
										ACAA[G/A]CC
										CAACTTGAT
										CGCTCACCG
										CCGCGTGCA
										CACGGGCGA
										GC
chr	150738	C	T	ABCB8	p.G40	0.005	0.002	5.50	1.9[1	TGCCCCCTG	SEQ
7	005				5G	64	97	E-	.24-	GCAAGATCG	ID
								03	2.91]	TGGCCCTCG	No:
										TGGGCCAGT	915
										CTGG[C/T]GG
										AGGTAAGGG
										GAGCCCACC
										ACCTCTTCA
										CCCTCTGAC
										TC
chr	150840	A	T	AGAP3	p.E431	0.005	0.002	1.04	1.85	TCATGCCCT	SEQ
7	440				D	15	79	E-	[1.19-	GATGGGCCT	ID
								02	2.88]	GTGGTTGCA	No:
										GAGAGGAGA	916
										AGGA[A/T]CG
										CTGGATACG
										GGCCAAGTA
										TGAACAGAA
										GCTCTTCCTG
										G
chr	151078	C	T	WDR86	p.G31	0.006	0.003	8.14	1.73	GAGGGACCT	SEQ
7	993				3S	86	98	E-	[1.18-	ACCTGGATG	ID
								03	2.54]	CAGTTGATG	No:
										ATGAATGTG	917
										TGGC[C/T]CC
										GGAACACCC
										TCCGCAGCT
										CTCCAGACT
										GCGCGTCGA
										AG
chr	151859	G	A	KMT2C	p.S358	0.005	0.003	4.53	1.58	TTTTTCCTCT	SEQ
7	899				8L	64	57	E-	[1.04-	GGGATTATA	ID
								02	2.41]	TCAGAATAC	No:
										AACTGAATG	918
										AGC[G/A]ATT
										GGGTTGATC
										CCGGATAAC
										TGTGTCCAT
										GGGTTATAG
										T
chr	623435	G	A	ERICH1	p.P306	0.027	0.000	7.40	1561	CTCCCCGGA	SEQ
8					L	21	02	E-	.55[3	GTCTGCACC	ID
								159	85.5	CTCTTCCTCC	No:
									8-	CCAGCCCAT	919
									6324	GTC[G/A]GGT
									.12]	CTTCCTCGCT
										GGCGTCCGC
										ACCGTCCTC
										CTCCCTGGT
chr	623519	A	C	ERICH1	p.I278	0.014	0.000	1.13	Inf	TTTACCGTCT	SEQ
8					S	71	00	E-		TCCTCCCCG	ID
								87		GCCCGTGTC	No:
										AGGTCTTCC	920
										TCA[A/C]TGG
										TGTCCACAC
										CGTCCTCCTC
										CCTGGCGTC
										TTTAACGTC
chr	623675	A	C	ERICH1	p.V22	0.024	0.000	1.64	Inf	CTCGCTAGC	SEQ
8					6G	51	00	E-		GTCCGCACC	ID
								145		ATCTTCCTCC	No:
										CTGGTATCTT	921
										TA[A/C]CGTC
										TTCCTCCCCG
										GCCAGTGTC
										GGGTCTTCC
										TCGCTGGT
chr	104660	A	C	RP1L1	p.D18	0.005	0.000	1.36	Inf	CTTCTGACTC	SEQ
8	31				59E	15	00	E-		TGGCTGGGC	ID
								30		CTCCCCTTCA	No:
										GCCTCCTGG	922
										GC[A/C]TCCC
										CTTCTGCCTC
										TGGGGCCTC
										TACACCTTCT
										GACTCTG
chr	171597	A	G	MTMR7	p.M52	0.005	0.002	1.04	1.85	TAGTTCTTCC	SEQ
8	18				2T	15	79	E-	[1.19-	TCTAGCTGC	ID
								02	2.88]	TGAGTTTCTT	No:
										CCTTCACTG	923
										CC[A/G]TTAG
										GTAATCTGT
										AACTGACTG
										TCGGGGCTG
										CATCCCCTT
chr	180803	A	T	NAT1	p.D25	0.005	0.003	1.32	1.76	ACCCTCACC	SEQ
8	08				1V	88	35	E-	[1.16-	CATAGGAGA	ID
								02	2.66]	TTCAATTAT	NO:
										AAGGACAAT	924
										ACAG[A/T]TC
										TAATAGAGT
										TCAAGACTC
										TGAGTGAGG
										AAGAAATAG
										AA
chr	234289	C	G	SLC25	p.T191	0.005	0.003	3.48	1.63	ACCGGTCAG	SEQ
8	24			A37	T	15	17	E-	[1.05-	CAATCAGCT	ID
								02	2.53]	GCATCCGGA	NO:
										CGGTGTGGA	925
										GGAC[C/G]G
										AGGGGTTGG
										GGGCCTTCT
										ACCGGAGCT
										ACACCACGC
										AGC
chr	251746	C	T	DOCK5	p.T469	0.010	0.007	4.77	1.38	GACAAAGGG	SEQ
8	10				M	78	86	E-	[1.01-	AAGAAGAAG	ID
								02	1.87]	ACGCCAAAG	NO:
										AATGTGGAG	926
										GTGA[C/T]GA
										TGTCTGTGC
										ACGATGAGG
										AGGGCAAGC
										TCTTGGAGG
										TG
chr	267219	C	T	ADRA	p.R166	0.006	0.003	2.42	1.74	GTTGATCTG	SEQ
8	90			1A	K	506	743	E-	[1.05-	GCAGATGGT	ID
								02	2.73]	CTCGTCCTC	NO:
										GGGGGCCGG	927
										CTGC[C/T]TC
										CAGCCGAAC
										AGGGGTCCA
										ATGGATATG
										ACCAGGGAG
										AG
chr	356480	G	A	UNC5D	p.T930	0.009	0.005	1.25	1.79	CCCTGGCCT	SEQ
8	09				T	07	08	E-	[1.28-	GTGCCCTTG	ID
								03	2.5]	AAGAGATTG	NO:
										GGAGGACAC	928
										ACAC[G/A]A
										AACTCTCAA
										ACATTTCAG
										AATCCCAGC
										TTGATGAAG
										CCG
chr	367933	T	C	KCNU1	p.N11	0.005	0.002	8.09	2.24	TATCATCTC	SEQ
8	75				29N	64	53	E-	[1.46-	AGATACCTT	ID
								04	3.43]	TAGGTGACA	NO:
										ATGCAAAAG	929
										AAAA[T/C]GA
										AAGGAAAAC
										TTCAGATGA
										GGTTTATGA
										TGAGGATCC
										CT
chr	376997	G	A	GPR12	p.K13	0.005	0.000	9.89	Inf	CGTACCCGC	SEQ
8	77			4	07K	64	00	E-		TCAACGCCG	ID
								29		CCAGCCTAA	No:
										ACGGCGCCC	930
										CCAA[G/A]G
										GGGGCAAGT
										ACGACGACG
										TCACCCTGA
										TGGGCGCGG
										AGG
chr	382600	C	T	LETM2	p.A33	0.006	0.003	4.19	1.56	AAGTTCCAA	SEQ
8	50				1V	13	94	E-	[1.04-	CTCCATCCCT	ID
								02	2.34]	TACATTTCTT	No:
										TCAGATAAT	931
										TG[C/T]CAAG
										GAAGGGGTG
										ACAGCATTG
										AGTGTATCA
										GAACTACAG
chr	382657	C	T	LETM2	p.T385	0.005	0.002	2.15	1.92	GTTTTTTACG	SEQ
8	55				M	205	716	E-	[1.08-	CCTAGACAC	ID
								02	3.18]	TCCAGGCCA	No:
										AATCACAAA	932
										TGA[C/T]GGC
										CCAGAACAG
										CAAGGCTAG
										TTCAAAAGG
										AGCATAAAG
										G
chr	523208	G	C	PXDN	p.L111	0.007	0.004	4.90	1.54	TAAGCCGCG	SEQ
8	32			L	8V	482	863	E-	[0.97-	GAGAAGAGC	ID
								02	2.34]	CTCTGGGTC	No:
										AGCTCAGGA	933
										CTGA[G/C]AA
										GGTAGGAGG
										GTGCCCGCC
										ATTTAGCAG
										CCACGCCAA
										AC
chr	550491	A	G	MRPL	p.R57	0.012	0.008	4.23	1.36	GAGAAGAGG	SEQ
8	31			15	G	01	88	E-	[1.02-	TAGAAAATG	ID
								02	1.81]	TGGCAGAGG	No:
										CCATAAAGG	934
										AGAA[A/G]G
										GCAAAGAGG
										AACCCGGCC
										CCGCTTGGG
										CTTTGAGGG
										AGG
chr	813991	C	T	ZBTB10	p.S36L	0.018	0.014	3.39	1.31	GGCGGCGGC	SEQ
8	52					87	49	E-	[1.03-	TCCACGAAC	ID
								02	1.67]	AATAACGCT	No:
										GGCGGGGAG	935
										GCCT[C/T]AG
										CTTGGCCTC
										CGCAGCCCC
										AGCCGAGAC
										AGCCCCCGC
										CG
chr	919530	G	A	NECA	p.A27	0.007	0.004	1.54	1.74	GATGTCTGT	SEQ
8	77			B1	1T	16	12	E-	[1.08-	GATAGAAGA	ID
								02	2.68]	GGACCTGGA	NO:
										AGAATTCCA	936
										GCTC[G/A]CT
										CTGAAACAC
										TACGTGGAG
										AGTGCTTCC
										TCCCAAAGT
										GG
chr	947463	C	G	RBM1	p.E777	0.005	0.000	7.19	Inf	GGCCGCCTG	SEQ
8	10			2B	Q	88	00	E-		AAATGCTCC	ID
								34		TGGGGCGGT	NO:
										CTCCGGAAG	937
										TGCT[C/G]CG
										GGGGCGGGC
										GCCTGAAAT
										GCTCTGGGG
										GTGGCCGCC
										TG
chr	978921	G	A	CPQ	p.M24	0.008	0.004	1.07	1.75	CCTGTATTA	SEQ
8	19				5I	133	667	E-	[1.12-	CGGTGGAAG	ID
								02	2.62]	ATGCAGAAA	NO:
										TGATGTCAA	938
										GAAT[G/A]GC
										TTCTCATGG
										GATCAAAAT
										TGTCATTCA
										GCTAAAGAT
										GG
chr	989912	A	G	MATN2	p.K35	0.006	0.000	2.40	Inf	CTTTGCCAG	SEQ
8	22				6R	86	00	E-		TGCCATGAA	ID
								41		GGATTTGCT	No:
										CTTAACCCA	939
										GATA[A/G]A
										AAAACGTGC
										ACAAGTAAG
										TTACACACA
										CATGCACAC
										ACA
chr	100832	A	G	VPS13	p.N29	0.008	0.005	7.31	1.65	ACTTTGTTG	SEQ
8	259			B	68S	33	07	E-	[1.17-	ATAGAACTT	ID
								03	2.34]	CTGCCCTGG	NO:
										GCCCTGCTT	940
										ATCA[A/G]TG
										AATCCAAAT
										GGGACCTCT
										GGCTATTTG
										AAGGAGAGA
										AA
chr	103573	G	A	ODF1	p.S228	0.005	0.000	4.61	Inf	TGCAGCCCC	SEQ
8	042				N	64	00	E-		TGCAACCCC	ID
								34		TGCAGCCCC	NO:
										TGCAACCCG	941
										TGCA[G/A]CC
										CATATGATC
										CTTGCAACC
										CGTGTTATC
										CCTGTGGAA
										GC
chr	104897	G	A	RPVIS2	p.R175	0.005	0.003	4.50	1.59	GGATCCATG	SEQ
8	928				R	64	56	E-	[1.04-	CTGAAGTGT	ID
								02	2.42]	CCCGAGCAC	NO:
										GGCATGAGA	942
										GAAG[G/A]C
										ATAGTGATG
										TTTCTTTGGC
										AAATGCTGA
										TCTGGAAGA
										TT
chr	125711	A	G	MTSS1	p.A62	0.009	0.006	1.95	1.52	CAGCCTCCA	SEQ
8	789				A	31	16	E-	[1.09-	TCTGCTTACC	ID
								02	2.1]	ACGTGTGTT	NO:
										GGTGGCCAT	943
										GTC[A/G]GCC
										ACTTTCTGA
										AAGGCGTCC
										AAGAAGGCA
										GCTGCTGCT
										A
chr	144297	G	A	GPIHB	p.G15	0.005	0.000	1.65	Inf	GTCCAGGAC	SEQ
8	314			P1	9D	39	00	E-		CCAACAGGC	ID
								32		AAGGGGGCA	NO:
										GGCGGCCCC	944
										CGGG[G/A]C
										AGCTCCGAA
										ACTGTGGGC
										GCAGCCCTC
										CTGCTCAAC
										CTC
chr	144874	G	C	SCRIB	p.P145	0.013	0.000	9.10	229.	AGCTTTGGC	SEQ
8	555				0R	97	06	E-	41[7	CGTCCGCAC	ID
								60	1.81-	CGGGGCGCC	NO:
									732.	ACCTCCCAG	945
									85]	GGGT[G/C]GG
										GGGGACGCC
										GGGCTCTGC
										CTGGGGAAG
										GGACAGGAC
										GT
chr	144940	C	T	EPPK1	p.A22	0.008	0.001	2.32	7.88	GCCTCAGGT	SEQ
8	621				67A	09	03	E-	[5.34-	TGCGCACGG	ID
								17	11.6	GGTCGATGA	NO:
									3]	CGAAGCCGG	946
										TGGC[C/T]GC
										CTGCGCCTC
										CAGCAGCAC
										CAGGGCCGT
										GCCGGGCCG
										CA
chr	144941	A	T	EPPK1	p.Y20	0.006	0.003	2.84	1.61	GTGTCCTCTT	SEQ
8	229				65N	13	82	E-	[1.07-	GTGGGCGGC	ID
								02	2.41]	ACCTCTCCT	NO:
										GCAGCTCTC	947
										GGT[A/T]CGA
										GACCTTCTCT
										TGCGTGTTC
										GGGTCCACA
										AACCGTTTC
chr	144993	G	A	PLEC	p.L359	0.008	0.006	3.15	1.46	TGCTCCTCG	SEQ
8	230				1L	82	04	E-	[1.05-	GGGATCAGG	ID
								02	2.05]	TCCGACTGC	NO:
										ATCACCTCC	948
										CACA[G/A]G
										GACATGGTG
										GAGCCGCCG
										TGGCTGCCG
										CCGCCGGGA
										ATG
chr	145736	C	G	RECQ	p.V11	0.011	0.000	2.26	1295	GTCAGCGGG	SEQ
8	853			L4	96V	52	01	E-	.85[1	CCACCTGCA	ID
								67	78.7	GGAGCTCTT	NO:
									5-	CCGTGGCCA	949
									9394	GGCC[C/G]AC
									.47]	CAGGGCATG
										GAAGCTCAG
										GTGCAGGTA
										TTTTCTCCAG
										A
chr	146157	C	T	ZNF16	p.S30	0.005	0.003	4.01	1.6[1	CATGTGAGA	SEQ
8	265				N	39	38	E-	.04-	CTTTTGGTGC	ID
								02	2.46]	TTTTTAAGG	NO:
										CTCGAGTTC	950
										TGG[C/T]TGA
										AGGCTTTTC
										CACATTCAT
										TACACATAT
										AAGGCCTCT
										C
chr	411793	C	G	GLIS3	p.E360	0.008	0.004	6.65	1.8[1	GCTGGTCGA	SEQ
9	3				D	133	527	E-	.15-	TGTGGACCT	ID
								03	2.7]	TCTCGATGT	NO:
										GCCGCACGA	951
										GCTC[C/G]TC
										CTGCTGGTC
										GTACAGGGC
										GCTGCAGTC
										GATCCAGCG
										GC
chr	601362	C	T	RANB	p.D66	0.006	0.002	5.81	2.36	CTCTGCTGG	SEQ
9	4			P6	2N	831	903	E-	[1.44-	TCTCCAAGA	ID
								04	3.68]	TTTACAAAT	NO:
										TGCCAGCCA	952
										TCAT[C/T]GT
										CACTCATAT
										TTTCCACATC
										CTGTGTGTCT
										AAGAGAGCA
chr	154230	C	T	SNAP	p.H43	0.013	0.000	1.53	117.	TCCAGAGTA	SEQ
9	04			C3	Y	73	12	E-	22[5	TGAGCTTCC	ID
								64	9.77-	CGAGCTAAA	NO:
									229.	TACGCGCGC	953
									91]	TTTC[C/T]AT
										GTGGGCGCC
										TTTGGGGAG
										CTGTGGCGG
										GGCCGTCTG
										CG
chr	190503	G	A	RRAG	p.Q22	0.007	0.004	1.55	1.64	CTACATTCTT	SEQ
9	23			A	2Q	11	34	E-	[1.13-	GGTTATTTCC	ID
								02	2.39]	CACTACCAG	NO:
										TGCAAAGAG	954
										CA[G/A]CGCG
										ACGTCCACC
										GGTTTGAGA
										AGATCAGCA
										ACATCATCA
chr	337948	A	C	PRSS3	p.K12	0.007	0.004	6.12	1.78	GACAGGATG	SEQ
9	24				T	35	13	E-	[1.22-	CACATGAGA	ID
								03	2.62]	GAGACAAGT	NO:
										GGCTTCACA	955
										TTGA[A/C]GA
										AGGGGAGGA
										GTGCGCCAT
										TGGTTTTCCA
										TCCTCCAGA
										T
chr	337967	G	T	PRSS3	p.G10	0.005	0.000	3.09	Inf	CCCTACCAG	SEQ
9	46				6V	15	00	E-		GTGTCCCTG	ID
								31		AATTCTGGC	No:
										TCCCACTTCT	956
										GCG[G/T]TGG
										CTCCCTCATC
										AGCGAACAG
										TGGGTGGTA
										TCAGCAGCT
chr	356741	G	A	CA9	p.G79	0.014	0.001	1.18	10.6	GCCCAGTGA	SEQ
9	91				R	46	37	E-	7[7.8	AGAGGATTC	ID
								35	9-	ACCCAGAGA	NO:
									14.4	GGAGGATCC	957
									3]	ACCC[G/A]GA
										GAGGAGGAT
										CTACCTGGA
										GAGGAGGAT
										CTACCTGGA
										GA
chr	358100	G	A	SPAG8	p.F433	0.005	0.003	2.25	1.67	GAGACAAGG	SEQ
9	94				F	88	53	E-	[1.1-	GTACTGGTG	ID
								02	2.52]	TTGAGAAGC	NO:
										TGCAGTTCTT	958
										CCG[G/A]AAT
										GGTGTGTCC
										AATGTCCTG
										ATGTTACTG
										ACACCCTGG
										A
chr	391092	C	T	CNTN	p.A76	0.022	0.000	4.31	1284	GGCCCCAGT	SEQ
9	17			AP3	9T	55	02	E-	.01[3	GTATAAGCT	ID
								131	16.2	GCTTCGGAA	NO:
									4-	TGTGGTCGG	959
									5213	CCTG[C/T]GT
									.39]	CTGTCATCA
										CAATCTGAG
										TGACTGGCA
										GGTGCTCCT
										TT
chr	776135	A	G	C9orf41	p.D29	0.009	0.006	3.33	1.44	TTGATTTGG	SEQ
9	39				5D	80	81	E-	[1.05-	ACTTACTGC	ID
								02	1.99]	ATTCTGAAT	NO:
										AAATCTCTT	960
										GAAA[A/G]TC
										TCCTGCTGTC
										ATAGAAAAG
										TTAGAACCA
										GGAGGAAGA
										C
chr	845625	A	G	SPATA	p.K77	0.012	0.000	2.19	Inf	GTGGGGAAT	SEQ
9	04			31D3	9R	25	00	E-		TATCAGGGA	ID
								72		TGCAGCCAG	No:
										GAGACTGCC	961
										CCAA[A/G]A
										AACCATCTC
										TTGCATGAT
										CCGGAGACA
										TCTTCAGAG
										GAG
chr	941725	C	T	NFIL3	p.M17	0.005	0.003	3.57	1.6[1	GTGGAGAGT	SEQ
9	07				0I	88	69	E-	.06-	GTTTAATGA	ID
								02	2.41]	CAGAAATAC	NO:
										AACTACTTG	962
										ACAC[C/T]AT
										CGAGGGTTC
										GTGCTCGTC
										CACAAATGA
										ACTCACATT
										GG
chr	960518	G	A	WNK2	p.A16	0.005	0.000	1.02	56.0	GCGGGGGGG	SEQ
9	69				48A	39	10	E-	7[23.	ACCTGGCCC	ID
								22	94-	TGCCCCCAG	NO:
									131.	TGCCTAAGG	963
									32]	AGGC[G/A]GT
										CTCAGGGCG
										TGTCCAGCT
										GCCCCAGCC
										CTTGGTGAG
										TA
chr	960814	C	T	C9orf1	p.R130	0.010	0.007	2.68	1.43	TGCCTGTGA	SEQ
9	33			29	H	54	41	E-	[1.05-	ATCCCTTCCT	ID
								02	1.94]	TGTACATGG	NO:
										TGGTCAGTG	964
										GCA[C/T]GGA
										ATCCCCAAT
										AGATTGTAT
										ATCTGAAGG
										AGAAAAATA
										A
chr	964390	C	A	PHF2	p.T992	0.022	0.001	8.06	20.0	CCTCCACCA	SEQ
9	19				T	30	14	E-	2[14.	CGCCAGCCT	ID
								65	5-	CTACCACCC	NO:
									27.6	CGGCCTCCA	965
									51]	CCAC[C/A]CC
										GGCCTCCAC
										CAGCACGGC
										CAGCAGCCA
										GGCCTCGCA
										GG
chr	970809	A	C	NUTA1	p.S689	0.007	0.000	5.91	16.6	AAGAGAGGT	SEQ
9	53			2F	A	84	47	E-	9[10.	CGCTTCTTG	ID
								24	5-	GACTTGCTG	No:
									26.5	GCAGGAGAA	966
									2]	GGTG[A/C]TG
										GGCTGAGGC
										CTCTTTTCTG
										AGCAGATGG
										AGACTGAAG
										A
chr	106889	C	T	SMC2	p.S867	0.005	0.003	3.42	1.63	CCTCACCAC	SEQ
9	571				L	15	16	E-	[1.05-	ATATTTTCTT	ID
								02	2.54]	TAATTTTTTT	No:
										GTTTTAGGA	967
										GT[C/T]AGTA
										AATAAAGCT
										CAAGAAGAG
										GTGACCAAG
										CAAAAAGAG
chr	113562	T	C	MUSK	p.V55	0.006	0.004	2.64	1.59	GAAACTGAG	SEQ
9	589				8A	62	17	E-	[1.08-	ACTAACAGG	ID
								02	2.35]	GATGGTCTT	No:
										TTGGTTCCA	968
										GGAG[T/C]GT
										GTGCTGTCG
										GGAAGCCAA
										TGTGCCTGC
										TCTTTGAAT
										AC
chr	117170	G	C	DFNB	p.P562	0.119	0.117	6.55	1.02	AACCAAAGG	SEQ
9	241			31	A	36	07	E-	[0.93-	GCCAGCCAG	ID
								01	1.13]	GGCCTTACC	No:
										ACGGACACA	969
										TCTG[G/C]GA
										GGGCGTTGA
										TATTGCCCT
										GGACAGCCT
										CGCCAGTTT
										CC
chr	127623	G	A	RPL35	p.R32	0.011	0.008	3.12	1.39	TAGAGAGCT	SEQ
9	742				R	76	52	E-	[1.03-	TGGAGGCCG	ID
								02	1.85]	CACCGCCTG	No:
										TCACTTTGG	970
										CGAC[G/A]CG
										CAGCTGGGA
										CAGCTCCAC
										CTTCAGGTC
										GTCCAGCTG
										TT
chr	131094	G	C	COQ4	p.E161	0.012	0.008	1.55	1.44	ATGATGAGG	SEQ
9	512				D	25	51	E-	[1.09-	AGCTAGCGT	ID
								02	1.92]	ATGTGATTC	No:
										AGCGGTACC	971
										GGGA[G/C]GT
										GCACGACAT
										GCTTCACAC
										CCTGCTGGG
										GATGCCCAC
										CA
chr	131258	G	C	ODF2	p.Q61	0.007	0.000	2.84	Inf	TAAACCAGT	SEQ
9	331				7H	84	00	E-		CTGTGTTCCT	ID
								47		GTCATTTTA	NO:
										GATCGAACA	972
										CCA[G/C]GGG
										GACAAGCTG
										GAGATGGCG
										AGAGAGAAA
										CATCAGGCT
										T
chr	132630	G	A	USP20	p.S288	0.005	0.003	9.34	1.85	ACCGGAGCC	SEQ
9	457				S	64	05	E-	[1.21-	CATCAGAAG	ID
								03	2.83]	ATGAGTTCT	NO:
										TGTCCTGTG	973
										ACTC[G/A]AG
										CAGTGACCG
										GGGTGAGGG
										TGACGGGCA
										GGGGCGTGG
										CG
chr	134353	G	A	PRRC2	p.E147	0.005	0.003	2.96	1.71	CTGGTTAAC	SEQ
9	141			B	3K	15	03	E-	[1.1-	AAGATCCTC	ID
								02	2.65]	TTTCCCTTAC	NO:
										AGATCCCCA	974
										GAC[G/A]AG
										GCCTTGCCT
										GGAGGTCTT
										AGTGGCTGC
										AGCAGTGGG
										AG
chr	135140	A	G	SETX	p.I254	0.008	0.005	2.68	1.5[1	GGGTTGTGG	SEQ
9	020				7T	58	72	E-	.07-	ATCCCAAAG	ID
								02	2.12]	GAATATTCC	NO:
										TCCTTTGACC	975
										TCA[A/G]TGC
										CCATCCTCTT
										CAGCAGTCG
										TGGGTCCTG
										AAGTTGGTC
chr	136419	G	A	ADAM	p.G42	0.023	0.000	1.28	Inf	CGAGCAGGC	SEQ
9	800			TSL2	1S	28	00	E-		CGGCGGCGG	ID
								12		GGCCTGCGA	NO:
										GGGGCCCCC	976
										CAGG[G/A]G
										CAAGGGCTT
										CCGAGGTAA
										CCAGGAGGA
										GGGAGGCAT
										GAG
chr	137309	G	A	RXRA	p.M25	0.006	0.003	2.76	1.62	CCGTGGAGC	SEQ
9	155				41	13	79	E-	[1.08-	CCAAGACCG	ID
								02	2.43]	AGACCTACG	NO:
										TGGAGGCAA	977
										ACAT[G/A]GG
										GCTGAACCC
										CAGCTCGGT
										GAGTTGCAG
										CCTGTGCAG
										GG
chr	139333	G	C	INPP5	p.G12	0.007	0.000	1.78	447.	TCAGGCAGG	SEQ
9	512			E	0G	11	02	E-	13[6	GCGGGGAGC	ID
								34	0.89-	AGCTGTGGG	No:
									3283	CGGGGGCCC	978
									.17]	CGGG[G/C]CC
										CTCGCTCTG
										CACTGAGCC
										CCTGGAGGG
										ACTGGTCCC
										AT
chr	139701	G	T	CCDC	p.M45	0.005	0.003	4.82	1.63	GCGAGGGGA	SEQ
9	301			183	71	856	603	E-	[0.95-	AGCTCACGT	ID
								02	2.61]	ACCTGGCTG	No:
										ACAGAGTGC	979
										AGAT[G/T]GT
										GTCCAGGAC
										CGAGGAGGT
										AGCCCCGGG
										CTGGGAGGA
										AC
chr	139752	A	T	NIAMD	p.T771	0.009	0.006	4.61	1.42	CTCGGGCCA	SEQ
9	023			C4	S	07	39	E-	[1.02-	TGCTGCCTG	ID
								02	1.98]	GGGCCCCCC	No:
										AACAGACCA	980
										TACC[A/T]CT
										GAGACAGCC
										CAAGGTATG
										GGGGCCTGG
										CAGGGGCAG
										GG
chr	140008	G	A	DPP7	p.Q38	0.005	0.000	4.86	Inf	TTGTTGCCG	SEQ
9	984				X	15	00	E-		AAGCGCTCG	ID
								28		AAGTTGAAG	No:
										TGGTCCAGA	981
										CGCT[G/A]CT
										GGAAGAAGC
										GCTCCTGGA
										AGCCGGGGT
										CCGGGGCCC
										TG
chr	140120	G	T	CYSRT1	p.A14	0.011	0.000	2.82	Inf	AGCGCCAGG	SEQ
9	397				8A	03	00	E-		CCGGACTGA	ID
								52		CCTACGCTG	No:
										GCCCTCCGC	982
										CCGC[G/T]GG
										GCGCGGGGA
										TGACATCGC
										CCACCACTG
										CTGCTGCTG
										CC
chr	986397	C	CT	SHRO	p.L676	0.005	0.000	2.57	61.9	CTGGAGGGC	SEQ
X	4			OM2	fs	89	10	E-	[12.5-	CGGGTTGGG	ID
								07	307.	AGGTGGCAC	No:
									11]	CCAGGAAGG	983
										ACCC[C/CT]T
										CGCTGGCAC
										CTATAAAGA
										CCACCTGAA
										AGAGGCCCA
										AGC
chr	100856	C	T	WWC3	p.H52	0.006	0.003	4.13	1.56	GGGACGAAG	SEQ
X	59				0H	13	94	E-	[1.03-	ACTTACCAG	ID
								02	2.36]	GCATGGCGG	NO:
										CCCTTCAGC	984
										CACA[C/T]GG
										GGTCCCCGG
										GGATGGGGA
										AGGGCCGCA
										CGAGCGAGG
										AC
chr	349618	G	A	FM4	p.P297	0.005	0.000	6.33	473.	GCCCGGAGC	SEQ
X	39			7B	P	88	01	E-	89[6	CTCCCGAGA	ID
								31	4.09-	CTCGCGTAT	NO:
									3503	CTCATCTCC	985
									.83]	ACCC[G/A]GA
										GCCTCCTGA
										GACTGGAGT
										GTCCCATCT
										CCGCCCAGA
										GC
chr	370279	C	G	FAM4	p.D49	0.006	0.000	5.71	Inf	CAGAGAAGG	SEQ
X	59			7C	2E	86	00	E-		ACGTATCTC	ID
								37		ATCTCCGCC	NO:
										CAGAGCCTC	986
										CCGA[C/G]AC
										TGGAGTGTC
										CCATCTCTG
										CCCAGAGCC
										CCCCAAGAC
										AC
chr	370287	C	T	FAM4	p.R763	0.008	0.000	2.98	692.	TCTCCGCCC	SEQ
X	70			7C	C	58	01	E-	67[9	AGAGCCTCT	ID
								45	4.87-	TGAGACTCG	No:
									5057	CGTATCTCA	987
									.22]	TCTC[C/T]GC
										CCGGAGCCT
										CCTGAGACT
										GGAGTGTCC
										CATCTCCAC
										CC
chr	436286	G	A	MAOB	p.T426	0.008	0.000	6.54	Inf	CAGCCCCCT	SEQ
X	23				T	82	00	E-		CCATGTAGC	ID
								48		CGCTCCAGT	NO:
										GTGTGGCAG	988
										TCTC[G/A]GT
										GCCTGCAAA
										GTAAATCCT
										GTCCACTGG
										CTGGCGTAG
										AA
chr	474267	C	T	ARAF	p.A33	0.010	0.007	3.68	1.42	TTGGCACCG	SEQ
X	57				7A	05	11	E-	[1.03-	TGTTTCGAG	ID
								02	1.95]	GGCGGTGGC	NO:
										ATGGCGATG	989
										TGGC[C/T]GT
										GAAGGTGCT
										CAAGGTGTC
										CCAGCCCAC
										AGCTGAGCA
										GG
chr	486648	C	T	HDAC	p.Y17	0.005	0.002	1.98	2.04	ACATGAATG	SEQ
X	50			6	1Y	88	90	E-	[1.34-	AGGGAGAAC	ID
								03	3.1]	TCCGTGTCCT	No:
										AGCAGACAC	990
										CTA[C/T]GAC
										TCAGTTTATC
										TGCATCCGG
										TATGGATGA
										GAACTCTGC
chr	491059	G	A	CCDC	p.D54	0.008	0.005	3.56	1.48	GCAGCCCAC	SEQ
X	70			22	6N	58	80	E-	[1.05-	TGATACCTTT	ID
								02	2.09]	GAGGTCCCT	No:
										GTGTCTGGT	991
										CAG[G/A]ATG
										CCAAGAAGG
										ACGATGCTG
										TTCGGAAGG
										CCTATAAGT
										A
chr	494559	C	T	PAGE1	p.G56	0.008	0.005	2.89	1.49	TTGGCTGAA	SEQ
X	76				G	82	92	E-	[1.06-	CCAGTTCCT	ID
								02	2.1]	GGCTATCAG	No:
										CTTCAGGCT	992
										CCTG[C/T]CC
										TTAAAGATA
										AAACAAAAT
										TATCATTTTA
										AGCAGCAAC
										A
chr	531153	G	A	TSPYL2	p.E607	0.009	0.006	2.37	1.5[1	AAGGCAGCG	SEQ
X	95				E	07	06	E-	.07-	ATGATGACG	ID
								02	2.1]	ACAGAGACA	No:
										TTGAGTACT	993
										ATGA[G/A]A
										AAGTTATTG
										AAGACTTTG
										ACAAGGATC
										AGGCTGACT
										ACG
chr	562918	A	G	KLF8	p.I108	0.009	0.006	4.00	1.43	CAAGGCTCC	SEQ
X	53				V	56	71	E-	[1.03-	TCTCCAGCC	ID
								02	1.98]	TGCTAGCAT	No:
										GCTACAAGC	994
										TCCA[A/G]TA
										CGTCCCCCC
										AAGCCACAG
										TCTTCTCCCC
										AGACCCTTG
										T
chr	708237	G	C	ACRC	p.K21	0.005	0.000	1.40	33.7	CCGACGACA	SEQ
X	81				8N	88	18	E-	6[17.	ACAGTGATG	ID
								22	45-	ATTCGGATG	No:
									65.3	TTCCCGACG	995
									11]	ACAA[G/C]A
										GTGATGATT
										CGGATGTTC
										CCGACGACA
										GCAGTGATG
										ATT
chr	738116	G	A	RLIM	p.S501	0.009	0.000	1.61	Inf	ATGTCGACC	SEQ
X	48				L	80	00	E-		CTCTCGCCT	ID
								52		GGCACCTGA	NO:
										TGAGCCTGA	996
										TGAT[G/A]AG
										CTTCCTTCAT
										TACTGCCTTC
										AAATAAATC
										TGAGCTAGT
chr	738116	A	G	RLIM	p.S485	0.010	0.000	6.36	46.1	CTTCATTACT	SEQ
X	95				S	29	23	E-	6[26.	GCCTTCAAA	ID
								41	25-	TAAATCTGA	No:
									81.1	GCTAGTTTCT	997
									6]	GA[A/G]CTTT
										CACCACCGG
										AACTGGAAC
										TAGGACTGG
										AACTGGAAC
chr	738117	C	T	RLIM	p.S453	0.010	0.000	2.96	825.	ACTCGAACT	SEQ
X	92				N	29	01	E-	58[1	GGAACTGGA	ID
								54	13.6-	ACTCGAACT	No:
									5999	GGAACCAGA	998
									.93]	ACTA[C/T]TA
										CCACCACCA
										GAACCTCCT
										CTTCCACTCC
										GTGACTCTG
										C
chr	100507	G	T	DRP2	p.L571	0.011	0.008	3.77	1.38	CCTGCTTCTT	SEQ
X	675				L	76	56	E-	[1.03-	GACAGGCAG	ID
								02	1.85]	GGCCAGCAA	No:
										AGGCAATAA	999
										GCT[G/T]CAC
										TACCCCATC
										ATGGAGTAT
										TACACACCG
										GTATGAAGC
										C
chr	100524	C	T	TAF7L	p.R372	0.011	0.007	2.26	1.44	TGTGGGCCA	SEQ
X	197				H	03	69	E-	[1.06-	CGCCAATGG	ID
								02	1.95]	CTCTCCTCAC	No:
										TTCTTCAGA	1000
										AAA[C/T]GCT
										GCAACTGTT
										CCTGTAGGG
										AAATGAGCT
										GTAGGGAGA
										G
chr	100745	C	G	ARMC	p.A77	0.008	0.000	8.99	Inf	CAGGGTGAG	SEQ
X	885			X4	0G	33	00	E-		GTCTTGCCT	ID
								34		GGTGCCAAA	NO:
										AATAAGGTC	1001
										AAGG[C/G]C
										AATCTTAAT
										GCTGTGTCT
										AAGGCAGAA
										GCTGGGATG
										GGT
chr	100746	G	C	ARMC	p.Q94	0.009	0.000	1.04	Inf	CTAAGGCAG	SEQ
X	423			X4	9H	31	00	E-		AGGCTGGGG	ID
								38		CAGGCATAA	NO:
										TGGGCTCTG	1002
										TCCA[G/C]GT
										CCAGGTTGT
										GGCCAGTTT
										TCAGGGTGA
										GGTCTTGCC
										TG
chr	101971	C	T	ARMC	p.S721	0.011	0.007	5.08	1.58	TGACTATTG	SEQ
X	960			X5-	S	52	33	E-	[1.17-	ACTATCACA	ID
				GPRA				03	2.13]	CACTGATTG	NO:
				SP2						CCAACTATA	1003
										TGTC[C/T]GG
										GTTTCTCTCC
										TTATTAACC
										ACAGCCAAT
										GCGAGAACG
										A
chr	102754	C	T	RAB40	p.E257	0.008	0.001	5.24	4.28	GTGCAGTTT	SEQ
X	916			A	K	33	96	E-	[2.95-	TTGGGTGGG	ID
								11	6.22]	CTCTGGGGT	NO:
										GGGCAGACG	1004
										ATCT[C/T]CA
										CTTTGCAGA
										GGCTGCTCT
										TGTGAGTGG
										AGCTGGTGG
										TG
chr	114425	G	A	RBA1X	p.R514	0.007	0.000	5.32	323.	AGCGACCGC	SEQ
X	545			L3	Q	60	02	E-	05[4	TACGGAGTA	ID
								32	4.09-	GGAGGCCAC	NO:
									2367	TATGAGGAG	1005
									.01]	AACC[G/A]A
										GGCCACTCT
										CTGGATGCC
										AACAGCGGA
										GGCCGTTCA
										CCC
chr	114426	C	T	RBA1X	p.Y84	0.012	0.000	4.17	101.	ACGCCTACA	SEQ
X	551			L3	9Y	01	12	E-	99[4	GTGGGGGCC	ID
								46	0.62-	GTGACAGTT	NO:
									256.	CCAGCAACA	1006
									12]	GTTA[C/T]GA
										CCGGAGCCA
										CCGCTATGG
										AGGAGGAGG
										CCACTACGA
										AG
chr	120008	G	C	CT47B1	p.P182	0.012	0.000	1.16	1046	CGACGCAGC	SEQ
X	980				R	99	01	E-	.3[14	CTCCTGGAT	ID
								68	4.66-	CAGGCCGAG	NO:
									7567	GCCCTCGCC	1007
									.63]	TTCT[G/C]GG
										GCTGCAGCC
										CCTGCACCC
										AGCCTCTGG
										GACAGCAGC
										AG
chr	124455	G	C	LOC10	p.K43	0.017	0.000	8.76	Inf	ACAGCCACA	SEQ
X	258			012952	0N	40	00	E-		GCATGAAGA	ID
				0				72		AAGATCCAG	NO:
										TGATGCCCC	1008
										AGAA[G/C]AT
										GGTCCCCCT
										GGGGGACAG
										CAACAGCCA
										CAGTCTGAA
										GA
chr	140993	A	G	MAGE	p.Q18	0.013	0.002	4.36	6.11	CTTTAGTGA	SEQ
X	751			C1	7Q	24	19	E-	[3.92-	GTATTTTCCA	ID
								16	9.52]	GAGTTCCCC	NO:
										TGAGAGTAC	1009
										TCA[A/G]AGT
										CCTTTTGAG
										GGTTTTCCCC
										AGTCTCCAC
										TCCAGATTC
chr	140994	T	A	MAGE	p.C501	0.014	0.000	9.16	Inf	CTCCTCCACT	SEQ
X	691			C1	S	71	00	E-		TTATTGAGT	ID
								80		CTTTTCCAG	No:
										AGTTCCCCT	1010
										GAG[T/A]GTA
										CTCAAAGTA
										CTTTTGAGG
										GTTTTCCCCA
										GTCTCCTCT
chr	149100	C	T	CXorf4	p.G15	0.009	0.005	1.69	1.54	AACATTCCT	SEQ
X	775			0B	5E	07	92	E-	[1.1-	TTCAGGAGC	ID
								02	2.15]	CCACACTTG	NO:
										TCACACTTC	1011
										ATGC[C/T]CC
										AAAGGGATC
										AGGTGCTCT
										GGGATGTCT
										ACCTGGAAT
										AC
chr	150908	G	T	CNGA2	p.G11	0.010	0.007	4.45	1.38	GGGCCTGAA	SEQ
X	168				3V	54	65	E-	[1.01-	CTCCAGACT	ID
								02	1.88]	GTGACCACA	NO:
										CAGGAGGGG	1012
										GATG[G/T]CA
										AAGGCGACA
										AGGATGGCG
										AGGACAAAG
										GCACCAAGT
										AC
chr	153295	C	T	MECP2	p.K44	0.018	0.000	3.45	Inf	TGGCGGCGG	SEQ
X	986				3K	87	00	E-		TGGCAACCG	ID
								102		CGGGCTGAG	NO:
										TCTTAGCTG	1013
										GCTC[C/T]TT
										GGGGCAGCC
										GTCGCTCTC
										CAGTGAGCC
										TCCTCTGGG
										CA

TABLE 2
Variants associated with infertility symptom of endometriosis
			Alter-
			nate		Amino	Chronic
		Refer-	Allele/		Acid	Pelvic	Infer-		OR
		ence	Minor		po-	Pain	tility		[L95-	Context	SEQ ID
Chr	Position	Allele	Allele	Gene	sition	MAF	MAF	p value	U95]	Sequence	NO
chr11	5444040	C	T	OR51Q1	p.L204F	0.0089	0.02899	2.59E-	0.30	CTGTGCTG	SEQ ID
						4		02		ACATCAGG	NO: 129
										CTCAACAG
										CTGGTATG
										GATTTGCT
										[C/T]TTGCC
										TTGCTCAT
										TATTATCG
										TGGATCCT
										CTGCTCAT
										TGT
chr19	53793162	C	T	BIRC8	p.A156T	0.0000	0.00725	1.16E-	0.00	GAAGTCTG	SEQ ID
						0		03		ATTCAATT	NO: 531
										CATTTTCT
										GTAGTGTC
										TTTCTGAG
										[C/T]GCTCA
										CTAGATCT
										GCAACAAG
										AACCTCAA
										GCGTTTTA
										TAG
chr2	238973062	A	G	SCLY	p.K60E	0.0000	0.00730	1.11E-	0.00	AACGACTC	SEQ ID
						0		03		CCCTGGAG	NO: 592
										CCAGAAGT
										TATCCAGG
										CCATGACC
										[A/G]AGGC
										CATGTGGG
										AAGCCTGG
										GGAAATCC
										CAGCAGCC
										CGTA
chr22	50315363	C	A	CRELD2	p.D182E	0.0282	0.06159	4.03E-	0.44	ACATGGGG	SEQ ID
						0		03		TACCAGGG	NO: 637
										CCCGCTGT
										GCACTGAC
										TGCATGGA
										[C/A]GGCT
										ACTTCAGC
										TCGCTCCG
										GAACGAG
										ACCCACAG
										CATCT
chr4	81967240	C	T	BHP3	p.T222M	0.0000	0.00725	1.16E-	0.00	GCCAAAGA	SEQ ID
						0		03		AAATGAAG	NO: 706
										AGTTCCTC
										ATAGGATT
										TAACATTA
										[C/T]GTCCA
										AGGGACGC
										CAGCTGCC
										AAAGAGG
										AGGTTACC
										TTTT

TABLE 3
Variants associated with pelvic pain symptom of endometriosis
			Alter-
			nate		Amino	Chronic
		Refer-	Allele/		Acid	Pelvic	Infer-		OR
		ence	Minor		po-	Pain	tility	p	[L95-	Context	SEQ ID
Chr	Position	Allele	Allele	Gene	sition	MAF	MAF	value	U95]	Sequence	NO
chr2	141232800	C	T	LRP1B	p.A3178T	0.	0.01087	7.31E-	0.00	GCCCAG	SEQ ID
						00000		05		TAGAGT	NO: 577
										CTACGA
										TTAACA
										TAATCT
										ATTGTT
										AGTG[C/
										T]CATA
										GGTCTA
										GAAATC
										TTGGTT
										TCTATG
										ACAACA
										CTCTGA
chr6	56033094	G	A	COL21L2A1	p.T343M	0.	0.11590	2.12E-	0.52	TACTAA	SEQ ID
						06389		03		GAGACG	NO: 786
										AATTTG
										GTGCCA
										GCCTTC
										ATCAAA
										CAAC[G/
										A]TCTA
										CAAAAA
										GAAAGT
										GTGGAA
										GATTCA
										TAAATA
										AAGCCC
chr6	85473758	C	T	TBX18	p.G48R	0.	0.57660	2.41E-	0.68	GCGCCG	SEQ ID
						48050		03		CCGCCG	NO: 789
										CGGCTG
										CAGCCT
										CCGTCG
										TCCACG
										GCCC[C/
										T]CGCC
										GCCTCT
										TCGGCG
										CCCAGT
										TTTCGC
										CGCTTC
										TTCTGA
chr9	117170241	G	C	DFNB31	p.P562A	0.	0.16060	4.01E-	0.59	AACCAA	SEQ ID
						10070		03		AGGGCC	NO: 969
										AGCCAG
										GGCCTT
										ACCACG
										GACACA
										TCTG[G/
										C]GAGG
										GCGTTG
										ATATTG
										CCCTGG
										ACAGCC
										TCGCCA
										GTTTCC

TABLE 4
Additional variants associated with endometriosis.
Endo-					L95	U95
metri-	Local				(lower	(upper
osis	pop-		OR		limit	limit
patient	ulation	gnomAD	(C	OR	95% con-	95%			Base				SEQ
Fre-	Control	Fre-	hisq	(odds	fidence	confidence			Pair	Minor	Major		ID
quency	Frequency	quency	test)	Ratio)	Interval)	Interval)	CHR	SNP	Position	Allele	Allele	Context Sequence	NO:
0.3055	0.28	0.2883	4.49E-	1.13	1.07	1.20	1	rs34108989	16,082,	C	T	GCATCAGGTATTTTTACCCACATT	SEQ
			05						127			TACCCCACCAGATTCT[T/C]GCTA	ID
												TGAAGCCACAAGGGACAAACCTG	NO:
												GGTTGGCAACCCC	1014
0.1844	0.1494	0.1591	1.75E-	1.29	1.20	1.38	1	rs2235529	22,450,	T	C	AAGCATCTGTGCCCCTAAAGCTG	SEQ
			12						487			ATGGCGGCTCCTCCAGC[C/T]TTC	ID
												TCTACCTGGTTCTGGTGTCCAGCC	No:
												CTTGGACTCCAGG	1015
0.2294	0.1992	0.2086	5.07E-	1.20	1.12	1.28	1	rs12042083	22,472,	A	G	CATGAGCCACCTTGCCTGGCCGG	SEQ
			08						732			AAATTCTTAATGAGAAA[G/A]TCT	ID
												CTTGGAGGAAATGCTCTTCTAAC	NO:
												TTTCAAGAACAGCC	1016
0.4374	0.4042	0.4205	1.07E-	1.15	1.09	1.21	1	rs4623666	22,480,	G	A	ATCTTCAGCCTCCTACCAGCAAC	SEQ
			06						312			TATGCACACAGAAGCCC[A/G]GC	ID
												CGGTATCCCCACAGAGGCAGACG	NO:
												CCCCGGCACTGCCTT	1017
0.1126	0.09637	0.09915	9.43E-	1.19	1.09	1.30	1	rs12061124	97,989,	T	C	AGTTGAAACTCACAAACTGCAGG	SEQ
			05						751			AATATAGTCATTGGGGT[C/T]CCT	ID
												TAGATGCAGAAAAGAAAATTAAC	No:
												TACAGCGAGTTATG	1018
0.3216	0.3487	0.3388	3.65E-	0.89	0.84	0.94	2	rs2349415	49,247,	T	C	AAAACTTTATTCATAAAAACAGG	SEQ
			05						832			TGTCAGGCTGGATTTGA[T/C]CCA	ID
												TTGGCTGTAGTTCAGTGACACTG	NO:
												TCCTAGATCGTGGA	1019
0.	0.07747	0.08625	1.24E-	1.26	1.15	1.38	2	rs17025778	98,637,	G	A	TCCGGGGAACACGATTCCACCCA	SEQ
09559			06						504			TCACTGGGTGCTAGGTC[A/G]AGG	ID
												GTTCAGTTCTATGTCCTTCAGCAC	NO:
												TTATGAAACTGAG	1020
0.1044	0.08778	0.09062	2.55E-	1.21	1.11	1.32	2	rs17026292	98,677,	A	G	GGATGAATGGAAACTTGATTCTC	SEQ
			05						164			TTAATACAGTCCACTTG[G/A]GCT	ID
												CCATTTGTCTTCACAGCAACCATT	NO:
												TGCTGGATTTATT	1021
0.4036	0.3744	0.3827	1.47E-	1.13	1.07	1.20	2	rs755503	135,	A	G	TATGCTTAGGAAATATGTATATA	SEQ
			05						144,			TGGGATATCTCAAAATA[A/G]GG	ID
									45			AAAAGTTGGAGTGAAGATTAAAA	No:
												TAGAAAATAACAAAA	1022
0.1662	0.188	0.1822	4.81E-	0.86	0.80	0.93	2	rs10177996	219,	C	T	CTATGTGAATGTGACTGAAACAT	SEQ
			05						746,			ATCTGTGGGAGTGGGCT[T/C]GTG	ID
									561			GGGAACCCTGTGTGTATGGGCAT	NO:
												CTATTCCTGGGGAT	1023
0.2852	0.259	0.263	1.47E-	1.14	1.08	1.21	2	rs388208	225,938,	T	C	ACAGTTAATATTGACTGCTTTGTT	SEQ
			05						996			CATTGATACATTCCCT[T/C]GACC	ID
												TAGACCATTGCTGGGCACATAGT	NO:
												AGGCTCTCAGTAA	1024
0.1818	0.1613	0.1695	5.28E-	1.16	1.08001	1.2425	3	rs6792001	6,106,	A	G	CTATTGATTTTTGAGGTAGATATT	SEQ
			05						251			GATGCAATTAGAGATA[A/G]GCTT	ID
												TAGGAAGATCTTCCTGGAAGTGG	NO:
												TATATAAATAGTT	1025
0.2338	0.258	0.2584	6.26E-	0.88	0.82	0.94	3	rs6777088	8,786,	G	A	CACCCTTCAGATCATAAAACAAT	SEQ
			05						487			AGAATTTGAGAGCTGCG[A/G]CT	ID
												ATAGCACTGCCACTAAGTCACTG	NO:
												TTGGCTTTAAGCAAG	1026
0.1513	0.1744	0.1682	1.05E-	0.84	0.78	0.91	3	rs4293672	25,913,	T	C	AATTGACACACTACTGAAAAGAA	SEQ
			05						415			AAGAGAATTAGAACAAC[T/C]TG	ID
												CCTGGAGTTAAAGTCCCTTAGTT	NO:
												AATGGATAAGTCACC	1027
0.1244	0.146	0.1344	9.21E-	0.83	0.77	0.90	3	rs16843225	100,801,	G	T	TCTGGTGTCATTAAGGAAGCAGG	SEQ
			06						257			TTACAGGCCAGCATATC[T/G]TCA	ID
												AATAGCTACACAGGTGTTAGAAC	NO:
												TGCATGGTCTTATA	1028
0.1405	0.1226	0.126	8.98E-	1.17	1.08	1.27	3	rs4680277	156,245,	A	G	GTGCTAATTATCCAGAATCAGCT	SEQ
			05						781			GCAGTTGCTACCATGGA[A/G]GTA	ID
												ACCAGCTCTGCCCAGTGGGTTCT	NO:
												CCTGTGCCCTACAG	1029
0.1399	0.1208	0.1259	2.78E-	1.18	1.09	1.28	3	rs6795731	156,	T	C	TAGTGAAGAAAACATCATGCTGG	SEQ
			05						262,			TTATGTTACCATTTTTC[C/T]CAGG	ID
									460			CAACCAGGGTTATGGAAGAAAG	NO:
												GACTCATTAATGGC	1030
0.2683	0.2988	0.288	1.43E-	0.86	0.81	0.92	4	rs12505096	56,006,	A	C	GATGTGGTCATATGAAGGCTTGA	SEQ
			06						102			CTGGGGCTGAAGAATAC[C/A]TTT	ID
												CTGGTGTGACTCACTCACATGAC	NO:
												TATTGGCAAGAGAA	1031
0.2068	0.1826	0.1907	6.96E-	1.17	1.09	1.25	4	rs10014285	161,	A	G	CCTTGGAGAGTTCCTCCACTTCTC	SEQ
			06						307,			TCTGACAATTAAAATC[G/A]GTGT	ID
									972			TTGCTGAGATTAGACATTTTTTTC	NO:
												TTCTCTGTTTAG	1032
0.04611	0.03563	0.0323	5.50E-	1.31	1.15	1.49	4	rs12650364	186,	A	G	TGGTGGTAGGGAGACCTTTTGGT	SEQ
			05						365,			GGTATTTGAATTAAACA[G/A]TAT	ID
									998			CATTTTCTTTAAAACCAACTCCAC	NO:
												AGACTACAAAAAT	1033
0.05481	0.0401	0.0479	1.06E-	1.39	1.23	1.57	4	rs4611976	188,	G	T	GTGTTGGTCGGTACAGTTCTAGA	SEQ
			07						990,			AGGAAAGCTCTGAGCTG[T/G]GC	ID
									955			CCCTCTCTCCAGGTGGAATTAGA	NO:
												TTTTATATATTCACT	1034
0.3727	0.3466	0.3437	7.34E-	1.12	1.06	1.19	5	rs4128741	76,423,	T	C	ATTCCCCATTCCTTTACAATTATA	SEQ
			05						967			ATTGCCTCCATATTGT[C/T]CAAG	ID
												GACCATAGTTACCACTTGACCCA	NO:
												GAGCCTCTCCCTT	1035
0.4173	0.3783	0.3939	6.02E-	1.15	1.09	1.22	5	rs12521058	76,	A	C	AGCTGTTCTCAGATACCAGACTG	SEQ
			07						426,			GAATAAACGAGAGACAT[C/A]TG	ID
									987			GAGAAAGGAGACCTCTTCCTATC	No:
												CCAACAGGACTGTGT	1036
0.1807	0.1566	0.1645	1.77E-	1.19	1.11	1.28	6	rs6456259	19,	G	A	GCTCACCAAGCAAGATTCCTCTC	SEQ
			06						761,			ATCCCCTGCCACTCCCT[A/G]TTT	ID
									718			AATGCCTTTGTAAAAACTGTAAT	NO:
												TTGGTGAATCCCAA	1037
0.1874	0.1659	0.1615	2.88E-	1.16	1.08	1.24	6	rs563440	151,	C	T	GCTACTCTTTTCTTCCAAAATACT	SEQ
			05						288,			CTCTCCTCAGCAGCCA[T/]AGAG	ID
									991			ACTGAAACCTAATGAAGCCCTGT	NO:
												TGCCTTCCTACTT	1038
0.1003	0.118	0.1262	6.95E-	0.83	0.76	0.91	6	rs9347099	166,	T	G	TCATTGGGAGTTATGAGCACATT	SEQ
			05						327,			TCATAAACATAATTCCA[G/T]GGG	ID
									886			TTCGCCTGTGATGACATCATTCCT	No:
												TTTCACAAGGTTT	1039
0.4488	0.4107	0.4152	2.01E-	1.17	1.11	1.23	7	rs11773804	27,	G	T	CTCCCCCTGCCCCCAATTCCTAAC	SEQ
			08						206,			AGAAAGCAGCGACTCC[T/G]AGA	ID
									688			ACAGGGGTAATCAAATTCACGTG	NO:
												TGGATACTGTGCCT	1040
0.1704	0.1916	0.1829	9.23E-	0.87	0.81	0.93	7	rs11535191	37,	G	A	AGGAAAATAAATTATGGAGACAT	SEQ
			05						747,			TAAGTAAATTGCCCAAG[A/G]TG	ID
									276			GCCCAGCTAGTAAATAATAAAGG	No:
												CAAGATTTTAGAGCC	1041
0.2479	0.2246	0.1985	5.67E-	1.14	1.07	1.21	8	rs17342242	60,	G	A	TAATGAATCTGAGTGGGATAGTG	SEQ
			05						828,			ATCAGAATAAGGAAGTA[A/G]GG	ID
									697			CCAATAACATTTCTGGGTAACTT	NO:
												GCCATGAGCCAAGCA	1042
0.06199	0.07925	0.08	2.88E-	0.77	0.69	0.86	9	rs9695167	106,	A	C	TTATAGTCCCAAGTAGTCAGAGA	SEQ
			06						169,			TGGACTGTATAATATGC[C/A]GGG	ID
									268			CACAGGGCAAAACAAGAATGAG	NO:
												GGAAGTTGTTGACAG	1043
0.3579	0.3919	0.3861	4.64E-	0.87	0.82	0.92	10	rs11253141	5,422,	C	A	AGCTATCATTCCCCAGTGTGAAC	SEQ
			07						196			CTCAAGTCATCAGATTG[A/C]ATC	ID
												TCCCCACCTGCCATTGTTTTTATC	NO:
												ACCTACCAACACC	1044
0.1681	0.1425	0.1327	1.62E-	1.22	1.13	1.31	10	rs11256106	9,222,	C	A	TGAAATTGAAGTGGTGTTTATGA	SEQ
			07						228			ATCACATATGATAGATT[A/C]GGC	ID
												AATTGAGTTATATTTTTATATCTG	NO:
												CTTATCTCTCTAA	1045
0.4008	0.3734	0.3694	4.37E-	1.12	1.06	1.19	13	rs7997707	46,	A	G	GGCTGGAGGTCGAAAGACTCTAA	SEQ
			05						360,			TCTGTTTCACTGTTTAC[G/A]TGTT	ID
									678			CAGTCAGTTCTCTCATTGGCAAA	NO:
												ATATTTATCTCAA	1046
0.1636	0.1848	0.1726	7.49E-	0.86	0.80	0.93	13	rs9317519	66,	C	T	TGTTAAGTTATTCCAATAATAAA	SEQ
			05						137,			ATGTCATCCATAGGTTA[T/C]TGT	ID
									562			CACGTTTTAATATAAGACTTCTA	NO:
												ATCAAATTCCTGGG	1047
0.1589	0.1395	0.1305	5.40E-	1.17	1.08	1.26	13	rs336237	110,	T	C	TGGCTTCTTCGCAACTTGCATAG	SEQ
			05						496,			AGGCTACCTCTGTGTCC[C/T]CTT	ID
									410			ATGGCTCGATAGCTCATTTCTTTT	No:
												TATCCCCAAATAA	1048
0.3534	0.3266	0.32	3.80E-	1.13	1.07	1.19	14	rs10498441	52,	G	A	ATAAACATAGTTATGCTTCATTA	SEQ
			05						544,			CTCTGGTACAGAAACCC[G/A]GTT	ID
									224			CATTAGCCATTCAGAATGATTGT	NO:
												GATATCCAAAATGA	1049
0.3145	0.2871	0.2855	1.36E-	1.14	1.07	1.21	14	rs7157151	52,	T	C	TGTATCCAACCATGGGAAAAAGA	SEQ
			05						571,			CTTAGCTACATTGTATA[T/C]ATT	ID
									583			TGATGAGTAACGTGTTTATAATA	NO:
												CAACAAAAAGTGAA	1050
0.1256	0.1087	0.1131	9.94E-	1.18	1.08	1.28	14	rs12586828	71,	T	C	TTGTGCTGCCTGAGAGGAGAGGG	SEQ
			05						186,			AGCATCTCACCATCTCC[C/T]GCC	ID
									513			TTGGTATCTTTTATTCTTTAGGAC	No:
												TCAGCTCAGGTTC	1051
0.4297	0.4609	0.4572	5.73E-	0.88	0.83	0.93	14	rs1951521	100,	G	A	AATAAGTGAAAGAACTAGCAGTG	SEQ
			06						743,			CAGCTAGTAAATCTAAC[G/A]TGG	ID
									421			TTCTTTTTTGACAACTGACACCAG	No:
												AACCCTTAATCAT	1052
0.3167	0.3436	0.3378	3.97E-	0.89	0.84	0.94	15	rs7181230	40,	G	A	AAAAAACCCTTACATTAGCATAA	SEQ
			05						360,			AATCTGTAACAGGAGTG[A/G]AA	ID
									741			TGGAAATACAAGTTCTTGGAGAG	No:
												AACGAAATAATGTAA	1053
0.5069	0.4794	0.4746	7.28E-	1.12	1.06	1.18	15	rs12442708	47,	C	T	TTGCCTTTAGGACAGGACTGTTCT	SEQ
			05						144,			TAGTCCTCTCCAGTTC[T/C]ACTCT	ID
									386			ATTGTAAAGTTTCTGAAAGTGCC	NO:
												TCAGGTATTTCA	1054
0.4955	0.466	0.4712	1.79E-	1.13	1.07	1.19	16	rs10852432	66,	C	T	AGAATCTTAGGCTCATTTTGCCC	SEQ
			05						402,			ACATGGACCCATGACTG[T/C]TCC	ID
									515			CTGTATCCTCTCTCTGCACCCCCT	NO:
												CAGTCACACTGAA	1055
0.1229	0.1049	0.1056	2.60E-	1.20	1.10	1.30	16	rs152828	72,	T	C	CAGTGTCTACATCACTGACCTCT	SEQ
			05						123,			GTGGTATTTCCTCCTGC[T/C]TAT	ID
									886			GACTGAGGGTAGAATCCTCTGGT	NO:
												CCTTTTTTCCCCAA	1056
0.3705	0.343	0.3488	2.69E-	1.13	1.07	1.19	17	rs8076465	66,	A	G	GAGCCAGGTCATAGATGTAGCTT	SEQ
			05						513,			GTTTTGAAGTCAAGTGC[A/G]TTC	ID
									025			CTGGAGATCCGGTTTTGAAATGG	No:
												GTCACTGTAAGGTG	1057
0.3709	0.3432	0.3475	2.45E-	1.13	1.07	1.19	17	rs2907373	66,	A	G	CCCTTAGCTTGTCAAGTTAGCCTG	SEQ
			05						533,			GCCAGAGTCTGGGGCC[A/G]ACT	ID
									655			GTTCCACTGGGCCGTCGACTATG	NO:
												ACACTCTGCTGTCC	1058
0.2337	0.2109	0.207	6.31E-	1.14	1.07	1.22	18	rs2175565	46,	G	A	GACGGTGAGGAGCGGGTGATGG	SEQ
			05						079,			GGTAATTCCCGGAATGCA[G/A]A	ID
									852			CTGTAACCAGGGCAGTCAGAACA	NO:
												AGGATTGTTAACCTGC	1059
0.3788	0.3525	0.3617	7.47E-	1.12	1.06	1.18	18	rs3900176	74,	T	C	GTGAGTCGCCACTGTTGGCTTATT	SEQ
			05						739,			TTATGTATTTGCATCG[T/C]TCCC	ID
									022			ATCTAAATGGGGATTCCCAGACT	NO:
												TCATAGGCCAGTA	1060
0.07172	0.05786	0.06164	2.35E-	1.26	1.13	1.40	20	rs6110759	15,	G	A	GTACTTATAAAGCAGCGGAATCT	SEQ
			05						693,			CCTGCTTTATGAACTTT[A/G]GTT	ID
									977			CTGGGCTTCAGCTCTGTATTAGTC	NO:
												TGTTCTCACACTG	1061
0.2432	0.22	0.2304	5.67E-	1.14	1.07	1.21	20	rs6043979	16,	C	A	AATTCTCAGATCCACCAGTGAGA	SEQ
			05						451,			CAGAAAACATAGGAGAC[A/C]GG	ID
									642			AAAAGAAGAATCAAATGGGAAG	No:
												TGGAAAAAAGACAGGG	1062
0.	0.01914	0.01663	8.72E-	1.46	1.24	1.73	21	rs11702826	41,	T	C	AAATGCTCCTAGAACTGCAAAAC	SEQ
02777			06						908,			ACCTAACTTATTCCAAA[C/T]TTT	ID
									935			CCGGATGAAAAGGCAGAGGATTT	NO:
												TCTACTCCCATTTC	1063
0.2375	0.2623	0.248	4.68E-	0.88	0.82	0.93	22	rs1296795	18,	G	A	TCTCTTTCCAGGTTAAATGTTGTT	SEQ
			05						021,			CATTGCGTCCTTTCCC[A/G]AAGA	ID
									760			GTCTGTTCCCATAGAGAAGCATG	No:
												GCACAAAGTGTGC	1064
0.077	0.09421	0.09076	1.61E-	0.80	0.73	0.89	22	rs736490	45,	T	C	CAGCCGATGGGCTCTGCCAGATT	SEQ
			05						338,			CCTGATCCACAGTAGGA[C/T]CCT	ID
									213			GGGGGCACCCTCTGCCCGAGGAC	No:
												CCTGGAACACACAG	1065

While exemplary embodiments of the disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the disclosure be limited by the specific examples provided within the specification. While the disclosure has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. Furthermore, it shall be understood that all embodiments of the disclosure are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is therefore contemplated that the disclosure shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting one or more genetic variants in said nucleic acid sample, wherein said one or more genetic variants are listed in Table 1, Table 2 or Table 3.

2. The method of claim 1, wherein said high throughput method comprises nanopore sequencing.

3. The method of claim 1 or 2, wherein said nucleic acid sample comprises RNA.

4. The method of claim 3, wherein said RNA comprises mRNA.

5. The method of claim 1 or 2, wherein said nucleic acid sample comprises DNA.

6. The method of claim 5, wherein said DNA comprises cDNA, genomic DNA, sheared DNA, cell free DNA, fragmented DNA, or PCR amplified products produced therefrom, or any combination thereof.

7. The method of claim 5, wherein said DNA comprises DNA from an endometriosis lesion or peritoneal fluid.

8. The method of any one of claims 1-7, wherein said one or more genetic variants comprise a genetic variant defining a minor allele.

9. The method of any one of claims 1-7, wherein said one or more genetic variants comprise at least about: 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 500, or more genetic variants defining minor alleles.

10. The method of any one of claims 1-9, wherein detection of said one or more genetic variants has an odds ratio (OR) for endometriosis of at least about: 1.5, 2, 5, 10, 20, 50, 100, or more.

11. The method of any one of claims 1-10, wherein said one or more genetic variants comprise a synonymous mutation, a non-synonymous mutation, a stop-gain mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof.

12. The method of any one of claims 1-11, wherein said one or more genetic variants comprise a protein damaging mutation.

13. The method of any one of claim 12, wherein said one or more genetic variants further comprise a protein damaging or loss of function variant in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof.

14. The method of any one of claims 1-12, wherein said one or more genetic variants are comprised in GAT2, CCDC169, CASP8AP2, POU2F3, CD19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR or a combination thereof.

15. The method of any one of claims 1-13, further comprising detecting one or more additional variants defining a minor allele listed in Table 4.

16. The method of any one of claim 1-15, wherein said one or more genetic variants are identified or weighted based on a predictive mathematical or computer programmed algorithm.

17. The method of any one of claims 1-16, wherein said one or more genetic variants are identified based on reference to a database.

18. The method of any one of claims 1-17, further comprising identifying said subject as having endometriosis or being at risk of developing endometriosis.

19. The method of claim 18, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

20. The method of any one of claims 18-19, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

21. The method of any one of claims 18-20, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%.

22. The method of any one of claims 18-21, wherein said subject is identified as having endometriosis.

23. The method of claim 22, wherein said subject is asymptomatic for endometriosis.

24. The method of claim 22, wherein said subject is symptomatic for endometriosis.

25. The method of any one of claims 18-21, wherein said subject is identified as being at risk of developing endometriosis.

26. The method of any one of claims 1-25, further comprising administering a therapeutic to said subject.

27. The method of claim 26, wherein said therapeutic comprises hormonal therapy, an advanced reproductive technology therapy, a pain managing medication, or any combination thereof.

28. The method of claim 26, wherein said therapeutic comprises hormonal contraceptives, gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn-RH) antagonists, progestin, danazol, or any combination thereof.

29. The method of any one of claims 26-28, wherein said therapeutic comprises a pain medication.

30. The method of claim 29, wherein said pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof.

31. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 1.

32. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 2.

33. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 3.

34. The method of any one of claims 1-33, further comprising identifying said subject as having endometriosis-associated infertility or being at risk of developing endometriosis-associated infertility.

35. The method of claim 34, further comprising administering assisted reproductive technology therapy to said subject.

36. The method of claim 35, wherein said assisted reproductive technology therapy comprises in vitro fertilization, gamete intrafallopian transfer, or any combination thereof.

37. The method of claim 34, further comprising administering intrauterine insemination or ovulation induction.

38. The method of any one of claims 1-37, wherein said subject is a mammal.

39. The method of claim 38, wherein said mammal is a human.

40. The method of any one of claims 2-39, wherein said nanopore sequencing is performed with a biological nanopore, a solid state nanopore, or a hybrid nanopore.

41. The method of any one of claims 1-40, wherein said one or more genetic variants further comprise a mutation in SEPT10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof.

42. The method of claim 41, wherein said one or more genetic variants comprise a mutation in SEPT10 and wherein said mutation comprises a missense mutation.

43. The method of claim 41, wherein said one or more genetic variants comprise a mutation in TNFRSF6B and wherein said mutation comprises a homozygous or hemizygous mutation.

44. The method of claim 41, wherein said one or more genetic variants comprise a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion.

45. The method of any one of claims 1-44, wherein the one or more variants are identified based on a predictive computer algorithm.

46. The method of claim 45, wherein said predictive computer algorithm is Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, or MetaLR.

47. The method of any one of claims 1-46, further comprising administering a hormonal therapy to said subject.

48. The method of claim 47, wherein the hormonal therapy comprises administration of hormonal contraceptives, gonadotropin-releasing hormone (GnRH) agonists, gonadotropin-releasing hormone (GnRH) antagonists, progestin, danazol, or any combination thereof.

49. The method of any one of claims 1-46, further comprising administering to the subject an assisted reproductive therapy.

50. The method of claim 49, wherein the assisted reproductive therapy comprises in vitro fertilization, intrauterine insemination, ovulation induction, gamete intrafallopian transfer, or any combination thereof.

51. The method of any one of claims 1-46, further comprising administering to the subject a pain medication.

52. The method of claim 51, wherein the pain medication comprises a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof.

53. The method of any one of claims 1-46, further comprising administering a therapeutic to the subject.

54. The method of claim 53, wherein the therapeutic comprises a regenerative therapy, a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof.

55. The method of claim 53, wherein the therapeutic comprises a non-steroidal anti-inflammatory, a hormone treatment, a dietary supplement, a cannabis-derived therapeutic or any combination thereof.

56. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises an at least partially hemp-derived therapeutic, an at least partially cannabis-derived therapeutic, a cannabidiol (CBD) oil derived therapeutic, or any combination thereof.

57. The method of claim 53, wherein the therapeutic comprises the medical procedure, and wherein the medical procedure comprises a laparoscopy, a laser ablation procedure, a hysterectomy or any combination thereof.

58. The method of claim 53, wherein the therapeutic comprises the regenerative therapy, and wherein the regenerative therapy comprises a stem cell, a cord blood cell, a Wharton's jelly, an umbilical cord tissue, a tissue, or any combination thereof.

59. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises cannabis, cannabidiol oil, hemp, or any combination thereof.

60. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition is formulated in a unit dose.

61. The method of claim 53, wherein the therapeutic comprises hormonal therapy, an advanced reproductive therapy, a pain managing medication, or any combination thereof.

62. The method of claim 53, wherein the therapeutic comprises a hormonal contraceptive, gonadotropin-releasing hormone (GnRH) agonist, gonadotropin-releasing hormone (GnRH) antagonist, progestin, danazol, or any combination thereof.

63. The method of any one of claims 1-62, wherein the subject is asymptomatic for endometriosis.

64. A kit comprising: one or more probes for detecting one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof in a sample.

65. The kit of claim 64, further comprising a control sample.

66. The kit of claim 64, wherein the control sample comprises one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof.

67. The kit of any one of claims 64-66, wherein the one or more probes comprise a hybridization probe or amplification primer.

68. The kit of any one of claims 64-67, wherein the one or more probes is configured to associate with a solid support.

69. The kit of any one of claims 64-68, wherein the kit further comprises instructions for use and wherein the instructions for use comprise high stringent hybridization conditions.

70. The kit of any one of claims 64-69, wherein the one or more probes is configured to hybridize to a target region of a nucleic acid of the sample, wherein the target region comprises one or more genetic variants.

71. A system comprising: (a) a computer processor configured to receive sequencing data obtained from assaying a sample, wherein the computer processor is configured to identify a presence or an absence of one or more genetic variants of Table 1, Table 2, Table 3 or any combination thereof in the sample, and (b) a graphical user interface configured to display a report comprising the identification of the presence or the absence of the one or more genetic variants in the sample.

72. The system of claim 71, wherein the computer processor comprises a trained algorithm.

73. The system of claim 71 or 72, wherein the computer processor communicates a result.

74. The system of claim 73, wherein the result comprises an identification of the presence or the absence of one or more genetic variants in the sample.

75. A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting a genetic variant in said nucleic acid sample, wherein said genetic variant comprises a mutation in SEPT10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof.

76. The method of claim 75, wherein said genetic variant is a mutation in SEPT10 and wherein said mutation comprises a missense mutation.

77. The method of claim 75, wherein said genetic variant is a mutation in TNFRSF6B and wherein said mutation comprises a homozygous or hemizygous mutation.

78. The method of claim 75, wherein said genetic variant is a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion.

79. The method of claim 75, wherein said high throughput method comprises nanopore sequencing.