SPLICE VARIANTS ASSOCIATED WITH NEOMORPHIC SF3B1 MUTANTS

Abstract
Splice variants associated with neomorphic SF3B1 mutations are described herein. This application also relates to methods of detecting the described splice variants, and uses for diagnosing cancer, evaluating modulators of SF3B1, and methods of treating cancer associated with mutations in SF3B1.
Description

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy, created on May 16, 2014, is named 12636.6-304 SL.txt and is 183 kilobytes in size.


RNA splicing, a highly regulated molecular event orchestrated by the spliceosome, results in the removal of intronic sequences from pre-mRNA to generate mature mRNA. Dysregulation of RNA splicing has been identified as a causative defect in several diseases. In addition, dysregulated splicing has been proposed to play an important role in tumorigenesis and resistance to therapy; however, the molecular causes of dysregulated splicing in cancer have remained elusive.


SF3B1 is a protein involved in RNA splicing. It forms part of the U2 snRNP complex which binds to the pre-mRNA at a region containing the branchpoint site and is involved in early recognition and stabilization of the spliceosome at the 3′ splice site (3′ss). A thorough and systematic analysis of the effects of SF3B1 mutations is needed to define their effects on RNA splicing in cells and may lead to novel therapeutic approaches for SF3B1 mutant cancers.


The description provided herein demonstrates that certain SF3B1 mutations result in neomorphic activity with the production of known and novel splicing alterations. In addition, lineage-specific splicing aberrations were identified in chronic lymphocytic leukemia (CLL), melanoma, and breast cancer. Furthermore, treatment of SF3B1-mutant cancer cell lines, xenografts, and CLL patient samples with modulators of SF3B1 reduced aberrant splicing and induced tumor regression.


SUMMARY

The methods described herein involve detecting or quantifying the expression of one or more splice variants in a cell containing a neomorphic mutant SF3B1 protein. Various embodiments of the invention include detecting or quantifying splice variants to determine whether a patient has a cancer with one or more neomorphic SF3B1 mutations. Additional embodiments include measuring the amount of a splice variant to evaluate the effects of a compound on a mutant SF3B1 protein. Further embodiments include methods of treating a patient who has cancer cells with a neomorphic mutant SF3B1 protein.


Various embodiments encompass a method of detecting one or more splice variants selected from rows 1-790 of Table 1 in a biological sample, comprising:


a) providing a biological sample suspected of containing one or more splice variants;


b) contacting the biological sample with one or more nucleic acid probes capable of specifically hybridizing to the one or more splice variants, and


c) detecting the binding of the one or more probes to the one or more splice variants.


In some embodiments, the one or more nucleic acid probes capable of specifically hybridizing to the one or more splice variants each comprise a label. In some embodiments, the method of detecting one or more splice variants selected from rows 1-790 of Table 1 in a biological sample further comprises contacting the biological sample with one or more additional nucleic acid probes, wherein the additional probes are each labeled with a molecular barcode.


Embodiments further encompass a method of modulating the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising applying an SF3B1-modulating compound to the target cell, wherein the target cell has been determined to express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.


Embodiments also encompass a method for evaluating the ability of a compound to modulate the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising the steps of:


a) providing a target cell having a mutant SF3B1 protein;


b) applying the compound to the target cell; and


c) measuring the expression level of one or more splice variants selected from row 1-790 of Table 1.


In some embodiments, the method for evaluating the ability of a compound to modulate the activity of a neomorphic mutant SF3B1 protein in a target cell further comprises the step of measuring the expression level of one or more splice variants selected from row 1-790 of Table 1 before step (b).


In some embodiments, the neomorphic mutant SF3B1 protein is selected from K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In some embodiments, the neomorphic mutant SF3B1 protein is selected from E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N.


In some embodiments, the step of measuring the expression level of one or more splice variants comprises using an assay to quantify nucleic acid selected from nucleic acid barcoding (e.g. NanoString®), RT-PCR, microarray, nucleic acid sequencing, nanoparticle probes (e.g. SmartFlare™), and in situ hybridization (e.g. RNAscope®).


In some embodiments, the step of measuring the expression level of one or more splice variants comprises measuring the number of copies of the one or more splice variant RNAs in the target cell.


In further embodiments, the compound is selected from a small molecule, an antibody, an antisense molecule, an aptamer, an RNA molecule, and a peptide. In further embodiments, the small molecule is selected from pladienolide and a pladienolide analog. In additional embodiments, the pladienolide analog is selected from pladienolide B, pladienolide D, E7107, a compound of formula 1:




embedded image


a compound of formula 2:




embedded image


a compound of formula 3:




embedded image


or a compound of formula 4:




embedded image


In some embodiments, the target cell is obtained from a patient suspected of having myelodysplastic syndrome, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, or acute myeloid leukemia. In some embodiments, the target cell is obtained from a sample selected from blood or a blood fraction or is a cultured cell derived from a cell obtained from a sample chosen from blood or a blood fraction. In some embodiments, the target cell is a lymphocyte.


In further embodiments, the target cell is obtained from a solid tumor. In some embodiments, the target cell is a breast tissue cell, pancreatic cell, lung cell, or skin cell.


In some embodiments, one or more of the aberrant variants are selected from rows 1, 7, 9, 10, 13, 15, 16, 18, 21, 24, 27, 28, 30, 31, 33, 34, 48, 51, 62, 65, 66, 71, 72, 81, 84, 89, 91, 105, 107, 121, 135, 136, 152, 178, 235, 240, 247, 265, 267, 272, 276, 279, 282, 283, 286, 292, 295, 296, 298, 302, 306, 329, 330, 331, 343, 350, 355, 356, 360, 364, 372, 378, 390, 391, 423, 424, 425, 426, 431, 433, 438, 439, 443, 445, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, 472, 500, 508, 517, 519, 521, 524, 525, 527, 528, 530, 533, 536, 540, 543, 548, 545, 554, 556, 559, 571, 573, 580, 582, 583, 597, 601, 615, 617, 618, 639, 640, 654, 657, 666, 670, 680, 727, 730, 750, 758, 767, or 774 of Table 1.


In some embodiments, one or more of the aberrant variants are selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1.


Embodiments further encompass a method for treating a patient with a neoplastic disorder, comprising administering a therapeutically effective amount of an SF3B1-modulating compound to the patient, wherein a cell from the patient has been determined to:


a) contain a neomorphic mutant SF3B1 protein; and


b) express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.


Additional embodiments are set forth in the description which follows.


It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a schematic diagram depicting modes of alternative splicing.



FIG. 2 is a graph depicting levels of gene expression for abnormally spliced genes across different cancers in patient samples.



FIG. 3 is a schematic diagram showing the locations of certain neomorphic mutations in the SF3B1 protein and corresponding coding regions of the SF3B1 gene.



FIG. 4 is a graph depicting levels of aberrant splice variants detected in RNA isolated from pancreatic, lung cancer, and Nalm-6 isogenic cell lines using a NanoString® assay. Data are represented as the mean of three replicates.



FIG. 5 is a set of western blot images that confirm overexpression of SF3B1 proteins in 293FT cells.



FIG. 6 is a graph depicting levels of aberrant splice variants in RNA isolated from 293FT cells expressing wild type SF3B1 (SF3B1WT) or mutant SF3B1 proteins, as measured in a NanoString® assay. Data are represented as the mean of three replicates.



FIG. 7 is a set of western blot images that confirm overexpression of SF3B1 proteins in 293FT cells.



FIG. 8 is a graph depicting levels of aberrant splice variants in RNA isolated from 293FT cells expressing SF3B1WT or mutant SF3B1 proteins, as measured in a NanoString® assay.



FIG. 9A depicts a set of western blot images showing expression of SF3B1 alleles before and after shRNA-knockdown in Panc 05.04 cells. FIG. 9B depicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc 05.04 cells before and after shRNA-knockdown of all SF3B1 alleles (“SF3B1PAN) or SF3B1WT or mutant SF3B1 (SF3B1MUT) alleles. qPCR data are represented as fold change relative to pLKO non-treated with doxycycline (mean±SD, n=3). Solid black, outlined, and gray bars indicate SF3B1PAN, SF3B1WT, and SF3B1MUT allele-specific qPCR data, respectively.



FIG. 10A depicts a set of western blot images showing expression of SF3B1 alleles before and after shRNA-knockdown in Panc 10.05 cells. FIG. 10B depicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc 10.05 cells before and after shRNA-knockdown of SF3B1 alleles. qPCR data are represented as fold change relative to pLKO non-treated with doxycycline (mean±SD, n=3). Solid black, outlined, and gray bars indicate SF3B1PAN, SF3B1WT, and SF3B1MUT allele-specific qPCR data, respectively.



FIGS. 11A and 11B are a set of graphs depicting levels of splice variants in Panc 05.04 (FIG. 11A) and Panc 10.05 cells (FIG. 11B) before and after shRNA-knockdown of SF3B1 alleles, as measured in a NanoString® assay. Data are represented as mean of three biological replicates.



FIG. 12 is a set of graphs depicting growth curves of Panc 05.04 cells before (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.



FIG. 13 is a set of graphs depicting growth curves of Panc 10.05 cells before (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.



FIGS. 14A and 14B are a set of images of culture plates showing colony formation of Panc 05.04 cells (FIG. 14A) and Panc 10.05 (FIG. 14B) cells before and after shRNA-knockdown of SF3B1 alleles.



FIGS. 15A and 15B are a set of graphs showing the level of splicing of pre-mRNA Ad2 substrate in nuclear extracts from (FIG. 15A) 293F cells expressing Flag-tag SF3B1WT or SF3B1K700E (left and right panels [circles and triangles], respectively) and (FIG. 15B) Nalm-6 (SF3B1WT) and Nalm-6 SF3B1K700E cells (left and right panels [circles and triangles], respectively) treated with varying concentrations of E7101. Data are represented as mean±SD, n=2.



FIG. 16A depicts a pair of graphs showing the binding of a radiolabeled E7107 analog to either SF3B1WT (circles, left panel) or SF3B1K700E (triangles, right panel) after incubation of the proteins with varying concentrations of E7107. FIG. 16B depicts upper panels, a pair of graphs showing the levels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA (inverted triangles) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) treated with varying concentrations of E7107, as measured by qPCR. FIG. 16B depicts lower panels, a pair of graphs showing the levels of abnormally spliced isoforms of abnormally spliced genes COASY (triangles) and ZDHHC16 (diamonds) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) treated with varying concentrations of E7107, as measured by qPCR. qPCR data in (FIG. 16B) are represented as mean±SD (n=3).



FIG. 17 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with E7107 for two or six hours, as measured in a NanoString® assay. Data are expressed as fold change from DMSO-only treatment



FIG. 18 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with E7107 for six hours, as measured by RNA-Seq analysis.



FIG. 19 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with the numbered compounds indicated above the graphs, as measured by RNA-Seq analysis.



FIG. 20 is set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells at varying times following treatment of cells with E7107, as measured by qPCR of RNA. Data are represented as mean±SD (n=3). The upper panels of FIG. 20 depict the levels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA (inverted triangles) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) detected at certain times after treatment with E7107. The lower panels of FIG. 20 depict the levels of abnormally spliced isoforms of abnormally spliced genes COASY (triangles) and ZDHHC16 (diamonds) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) detected at certain times after treatment with E7107. Open circles show the concentration of E7107 (in μg/ml [right vertical axis]) as determined by mass spectrometry of tumor samples.



FIG. 21 is a set of graphs depicting levels of canonical and aberrant splice variants in Nalm-6 SF3B1K700K- and Nalm-6 SF3B1K700E-xenograft tumors (left and right sets of panels, respectively) at certain timepoints after treatment of xenograft mice with E7107, as measured in a NanoString® assay. Data are represented as mean of three replicates.



FIG. 22 is a set of graphs depicting levels of canonical and aberrant splice variants in Panc 05.04-xenograft tumors at certain timepoints after treatment of xenograft mice with E7107 at various concentrations, as measured in a NanoString® assay (n=4 mice for each group).



FIG. 23 is a graph depicting tumor volume (shown as mean±SEM) in Nalm-6 SF3B1K700E-xenograft mice following treatment with E7107, with control mice treated with vehicle shown by open circles (n=10 animals for each group). For E7107-treated animals, inverted triangles=1.25 mg/kg, triangles=2.5 mg/kg, and squares=5 mg/kg.



FIG. 24 is a graph depicting survival rates in 10-animal cohorts of Nalm-6 SF3B1K700E-xenograft mice following treatment with E7107, with an untreated cohort shown by the solid black line. For E7107-treated animals, dashed line=1.25 mg/kg, gray line=2.5 mg/kg, and dotted line=5 mg/kg.



FIG. 25 is set of graphs depicting levels of splice variants in SF3B1WT and neomorphic SF3B1 mutant CLL cell samples following treatment with 10 nM E7107 for 6 hours, as measured by analysis. Data are represented as mean values (n=3).





DESCRIPTION OF THE EMBODIMENTS

In certain aspects, the methods of the invention provide assays for measuring the amount of a splice variant in a cell, thereby determining whether a patient has a cancer with a neomorphic SF3B1 mutation. In some embodiments, at least one of the measured splice variants is an aberrant splice variant associated with a neomorphic mutation in an SF3B1 protein. In additional aspects, the measurement of a splice variant in a cell may be used to evaluate the ability of a compound to modulate a mutant neomorphic SF3B1 protein in a cell.


To assist in understanding the present invention, certain terms are first defined. Additional definitions are provided throughout the application.


As used herein, the term “mutant SF3B1 protein” includes SF3B1 proteins that differ in amino acid sequence from the human wild type SF3B1 protein set forth in SEQ ID NO:1200 (GenBank Accession Number NP_036565, Version NP_036565.2) (S. Bonnal, L. Vigevani, and J. Valcárcel, “The spliceosome as a target of novel antitumour drugs,” Nat. Rev. Drug Discov. 11:847-59 [2012]). Certain mutant SF3B1 proteins are “neomorphic” mutants, which refers to mutant SF3B1 proteins that are associated with differential expression of aberrant splice variants. In certain embodiments, neomorphic SF3B1 mutants include K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In other embodiments, neomophic SF3B1 mutants include E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. Certain SF3B1 mutations are not associated with expression of aberrant splice variants, including K700R.


The term “splice variant” as used herein includes nucleic acid sequences that span a junction either between two exon sequences or across an intron-exon boundary in a gene, where the junction can be alternatively spliced. Alternative splicing includes alternate 3′ splice site selection (“3′ss”), alternate 5′ splice site selection (“5′ss”), differential exon inclusion, exon skipping, and intron retention (FIG. 1). Certain splice variants associated with a given genomic location may be referred to as wild type, or “canonical,” variants. These splice variants are most abundantly expressed in cells that do not contain a neomorphic SF3B1 mutant protein. Additional splice variants may be referred to as “aberrant” splice variants, which differ from the canonical splice variant and are primarily associated with the presence of a neomorphic SF3B1 mutant protein in a cell. Aberrant splice variants may alternatively be referred to as “abnormal” or “noncanonical” splice variants. In certain circumstances, cells with a wild type or non-neomorphic SF3B1 protein have low or undetected amounts of an aberrant splice variant, while cells with a neomorphic SF3B1 protein have levels of an aberrant splice variant that are elevated relative to the low or undetected levels in the wild type SF3B1 cells. In some cases, an aberrant splice variant is a splice variant that is present in a wild type SF3B1 cell but is differentially expressed in a cell that has a neomorphic SF3B1 mutant, whereby the latter cell has a level of the aberrant splice variant that is elevated or reduced relative to the level in the wild type SF3B1 cell. Different types of cells containing a neomorphic SF3B1 mutant, such as different types of cancer cells, may have differing levels of expression of certain aberrant splice variants. In addition, certain aberrant splice variants present in one type of cell containing a neomorphic SF3B1 mutant may not be present in other types of cells containing a neomorphic SF3B1 mutant. In some cases, patients with a neomorphic SF3B1 mutant protein may not express an aberrant splice variant or may express an aberrant splice variant at lower levels, due to low allelic frequency of the neomorphic SF3B1 allele. The identity and relative expression levels of aberrant splice variants associated with various types of cells containing neomorphic SF3B1 mutants, such as certain cancer cells, will be apparent from the description and examples provided herein.


The term “evaluating” includes determining the ability of a compound to treat a disease associated with a neomorphic SF3B1 mutation. In some instances, “evaluating” includes determining whether or to what degree a compound modulates aberrant splicing events associated with a neomorphic SF3B1 protein. Modulation of the activity of an SF3B1 protein may encompass up-regulation or down-regulation of aberrant splice variant expression associated with a neomorphic SF3B1 protein. Additionally, “evaluating” includes distinguishing patients that may be successfully treated with a compound that modulates the expression of splice variants associated with a neomorphic SF3B1 protein.


The use of the word “a”, “an” or “the” when used in conjunction with the term “comprising” in the claims or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” “Or” is to be read inclusively to mean “and/or” unless explicitly indicated to refer to alternatives only, such as where alternatives are mutually exclusive.


Splice Variants


Splice variants of the invention are listed in Table 1. Table 1 provides the genomic location of each canonical (“WT”) and aberrant (“Ab.”) splice junction, as well as the sequence. Each sequence listed in the table contains 20 nucleotides from each of the 3′ and 5′ sides of a splice junction (i.e., the splice junction is at the midpoint of the listed nucleotide sequence). The “Avg WT %” and “Avg Ab. %” columns provide the average percentage count that the canonical (WT) or aberrant splice variant, respectively, represented out of the total counts of all splice variants that utilize a shared splice site, where the counts were determined as set forth in Example 1. The “Log2 Fold Change” column provides the log2 of the fold change observed between percentage counts of canonical and aberrant cohorts (see Example 1). The “FDR Q-Value” column provides, as a measure of statistical significance, q-values calculated using the Benjamin-Hochberg procedure from p-values, which in turn were determined using the moderated t-test defined in the Bioconductor's limma package (see Example 1). The “Event” column indicates the nature of the aberrant splice variant, where “3′ss” indicates alternate 3′ splice site selection, “5′ss” indicates alternate 5′ splice site selection, “exon incl.” indicates differential exon inclusion, and “exon skip” indicates exon skipping. The “Type” column refers to the cancer type of the sample in which the aberrant splice variant was identified, where “Br.” indicates breast cancer, “CLL” indicates chronic lymphocytic leukemia, and “Mel.” indicates melanoma.



















TABLE 1








Aberrant
WT


Log2






Aberrant

sequence
sequence
Avg WT
Avg Ab.
Fold
FDR Q-





junction 
WT junction
(SEQ ID NO)
(SEQ ID NO)
%
%
 Diff.
Value
Event
Type

























1
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
0
56
5.83
6.30E−07
3′ss
Br.



109102364-
109102364-
TCTATAAAATTT
TCTATAAAATAC









109102954
109102966
ACCCCCAGATAC
AGCTGGCTGAAA











AGCT (1)
TAAC (2)











2
chr16:
chr16:
CGGGCCGCATCA
CGGGCCGCATCA
0
51
5.70
2.38E−07
3′ss
Br.



708344-
708344-
TCCGGGAGAGCA
TCCGGGAGCTGC









708509
708524
CTGTGTTCCAGC
CCGGTGTCCACC











TGCC (3)
CTGA (4)











3
chr3:
chr3:
CTGGAGCCGGCG
CTGGAGCCGGCG
0
51
5.70
2.19E−07
3′ss
Br.



50380021-
50380000-
GGAAGGAGTGTG
GGAAGGAGGCAA









50380348
50380348
CTGGTTCCTCTC
GCTGCAGCAGTT











CCCA (5)
CGAG (6)











4
chr19:
chr19:
GGCCCTTTTGTC
GGCCCTTTTGTC
0
48
5.61
2.32E−06
3′ss
Br.



57908542-
57908542-
CTCACTAGCATT
CTCACTAGGTTC









57909780
57909797
TCTGTTCTGACA
TTGGCATGGAGC











GGTT (7)
TGAG (8)











5
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
47
5.58
7.79E−07
3′ss
Br.



97285513-
97285499-
GTCAACAGAGTT
GTCAACAGGACT









97297048
97297048
TCCCTTATAGGA
GGCTGGACAATG











CTGG (9)
GCCC (10)











6
chr19:
chr19:
GATGGTGGATGA
GATGGTGGATGA
0
46
5.55
1.10E−05
3′ss
Br.



23545541-
23545527-
ACCGACAGTTTT
ACCCACAGGTAT









23556543
23556543
TTTTTTTCAGGT
ATGTCCTCATTT











ATAT (11)
TCCT (12)











7
chr10:
chr10:
TACCTCTGGTTC
TACCTCTGGTTC
0
46
5.55
3.63E−09
3′ss
Br.



99214556-
99214556-
CTGTGCAGTCTT
CTGTGCAGTTCT









99215395
99215416
CGCCCCTCTTTT
GTGGCACTTGCC











CTTA (13)
CTGG (14)











8
chr18:
chr18:
TTGGACCGGAAA
TTGGACCGGAAA
0
44
5.49
4.30E−09
3′ss
Br.



683395-
683380-
AGACTTTGAGTC
AGACTTTGATGA









685920
685920
TCTTTTTGCAGA
TGGATGCCAACC











TGAT (15)
AGCG (16)











9
chr17:
chr17:
ACCCAAGCCTTG
ACCCAAGCCTTG
0
44
5.49
1.50E−07
exon
Br.



40714237-
40714237-
AGGTTTCATTTC
AGGTTTCAGCCT




incl.




40714373
40714629
CCCCTCCCAGGA
GGGCAGCATGGC











TTTC (17)
CGTA (18)











10
chr5:
chr5:
AGCATTGCTAGA
AGCATTGCTAGA
0
41
5.39
4.86E−09
3′ss
Br.



139815842-
139815842-
AGCAGCAGCTTT
AGCAGCAGGAAT









139818078
139818045
TGCAGATCCTGA
TGGCAAATTGTC











GGTA (19)
AACT (20)











11
chr1:
chr1:
CAAGTATATGAC
CAAGTATATGAC
0
39
5.32
1.31E−10
3′ss
Br.



245246990-
245246990-
TGAAGAAGATCC
TGAAGAAGGTGA









245288006
245250546
TGAATTCCAGCA
GCCTTTTTCTCA











AAAC (21)
AGAG (22)











12
chr3:
chr3:
TGCAGTTTGGTC
TGCAGTTTGGTC
0
36
5.21
9.63E−09
3′ss
Br.



9960293-
9960293-
AGTCTGTGCCTT
AGTCTGTGGGCT









9962150
9962174
CCTCACCCCTCT
CTGTGGTATATG











CCTC (23)
ACTG (24)











13
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
29
4.91
3.27E−07
3′ss
Br.



101458310-
101458296-
CTAATCAATTTT
CTAATCAAGGGA









101460665
101460665
CTGCCTATAGGG
AGGAAGATCTAT











GAAG (25)
GAAC (26)











14
chr7:
chr7:
GTATCAAAGTGT
GTATCAAAGTGT
0
28
4.86
5.02E−05
3′ss
Br.



94157562-
94157562-
GGACTGAGATTT
GGACTGAGGATT









94162500
94162516
GTCTTCCTTTAG
CCATTGCAAAGC











GATT (27)
CACA (28)











15
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
27
4.81
1.50E−07
3′ss
Br.



62701988-
62701988-
ACACACAGCCCT
ACACACAGGTGC









62703210
62703222
GTTCACAGGTGC
AGACCCGCAGCT











AGAC (29)
CTGA (30)











16
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
25
4.70
9.63E−06
3′ss
Br.



71198039-
71198039-
TTGTGAAATCAT
TTGTGAAAGTTT









71199162
71199138
TACTTCTAGATG
TGATTCATGGAT











ATGC (31)
TCAC (32)











17
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
0
25
4.70
5.99E−08
3′ss
Br.



7131030-
7131102-
CCCCCGAACCTA
CCCCCGAAATGA









7131295
7131295
TCCAGGTTCCTC
GCCCATCCAGCC











CTCC (33)
AATT (34)











18
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
25
4.70
2.72E−07
3′ss
Br.



35282126-
35282104-
GGGCTACATCCC
GGGCTACATACC









35284762
35284762
CTTGGTTCTCTG
ATCTGCCAGCAT











TTAC (35)
GACT (36)











19
chr2:
chr2:
TGACCACGGAGT
TGACCACGGAGT
0
25
4.70
1.61E−06
3′ss
Br.



232196609-
232196609-
ACCTGGGGCCCT
ACCTGGGGATCA









232209660
232209686
TTTTTCTCTTTC
TGACCAACACGG











CTTC (37)
GGAA (38)











20
chr17:
chr17:
AGACCTACCAGA
AGACCTACCAGA
0
24
4.64
7.16E−06
3′ss
Br.



62574712-
62574694-
AGGCTATGTGTT
AGGCTATGAACA









62576906
62576906
TATTAATTTTAC
GAGGACAACGCA











AGAA (39)
ACAA (40)











21
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
0
23
4.58
8.14E−08
3′ss
Br.



105601825-
105601807-
TAGCAATGATGT
TAGCAATGAGCA









105601935
105601935
CTGTTTATTTTT
TGACCTCTCAAT











AGAG (41)
GGCA (42)











22
chr12:
chr12:
CATGTGGAATCC
CATGTGGAATCC
0
22
4.52
1.87E−04
3′ss
Br.



53836517-
53836517-
CAATGCCGGCCC
CAATGCCGGGCA









53837270
53837174
CTGTCCTCCTCC
GCCAGGGCCAAA











CCCA (43)
TCCA (44)











23
chr22:
chr22:
CTGGGAGGTGGC
CTGGGAGGTGGC
0
22
4.52
2.76E−08
3′ss
Br.



19044699-
19044675-
ATTCAAAGCCCC
ATTCAAAGGCTC









19050714
19050714
ACCTTTTGTCTC
TTCAGAGGTGTT











CCCA (45)
CCTG (46)











24
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
0
21
4.46
4.61E−08
3′ss
Br.



71939542-
71939542-
TGCCTCAGTCAC
TGCCTCAGATGG









71939690
71939770
TTTACAGCTGCA
GGAGGATGAGAA











TCGT (47)
GCCC (48)











25
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
21
4.46
2.63E−08
3′ss
Br.



34144042-
34144042-
ACGGAGAGGCTC
ACGGAGAGGTAC









34144725
34144743
CCCTCCCACCCC
TGAGGACAAATC











AGGT (49)
AGTT (50)











26
chr6:
chr6:
AGAGAAGTCGTT
AGAGAAGTCGTT
2
64
4.44
2.91E−10
3′ss
Br.



31919381-
31919381-
TCATTCAAGTCA
TCATTCAAGTTG









31919565
31919651
GCTAAGACACAA
GTGTAATCAGCT











GCAG (51)
GGGG (52)











27
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
20
4.39
9.99E−07
3′ss
Br.



179835004-
179834989-
TAAACGAGTTTT
TAAACGAGGTAT









179846373
179846373
ATCATTTACAGG
GTGACGCATTCC











TATG (53)
CAGA (54)











28
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
0
20
4.39
1.35E−09
3′ss
Br.



52880319-
52880319-
AGGAGAAGTCTG
AGGAGAAGCCCC









52880412
52880433
ACCAGTCTTTTC
TCCCCTCGCCGA











TACA (55)
GAAA (56)











29
chr8:
chr8:
TTATTTTACACA
TTATTTTACACA
0
20
4.39
1.49E−09
3′ss
Br.



38095145-
38095145-
ATCCAAAGCCAG
ATCCAAAGCTTA









38095624
38095606
TTGCAGGGTCTG
TGGTGCATTACC











ATGA (57)
AGCC (58)











30
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
19
4.32
2.37E−05
3′ss
Br.



14031735-
14031735-
TCACCAAGCCTC
TCACCAAGGTGC









14034130
14034145
GTCCTCCCCAGG
CGCCTGCCCCTG











TGCC (59)
TCAA (60)











31
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
18
4.25
1.65E−10
3′ss
Br.



74358911-
74358911-
AACCAGAGTGTT
AACCAGAGCTCC









74360478
74360499
GTCTTTTCTCCC
TGGTACAGTTTG











CCCA (61)
TTCA (62)











32
chr19:
chr19:
ATATGCTGGAAT
ATATGCTGGAAT
0
18
4.25
8.07E−08
3′ss
Br.



45314603-
45314603-
GGTTCCTTGTCA
GGTTCCTTACCG









45315482
45315419
CAATGCACGACA
ACCGCTCGGGAG











CCCG (63)
CTCG (64)











33
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
0
18
4.25
4.25E−08
3′ss
Br.



212515622-
212515622-
TACAACAGGTTT
TACAACAGCTCC









212519131
212519144
CTTTTAAAGCTC
TGGAGCTTTTTG











CTGG (65)
ATAG (66)











34
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
18
4.25
1.31E−10
3′ss
Br.



125759640-
125759640-
TCCTAAAGCCTC
TCCTAAAGATAA









125760854
125760875
TCTCTTTCTTTG
AGTCCTGTTTAT











TTTA (67)
GACC (68)











35
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
0
17
4.17
1.35E−06
3′ss
Br.



4104212-
4104212-
ACAGCTAATTCT
ACAGCTAAGCAA









4104471
4104492
CTTTCCTCTGTC
GCACTGAGCGAG











TTCA (69)
GTGA (70)











36
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
0
17
4.17
3.58E−07
3′ss
Br.



113346629-
113346629-
TGCCCTGGATTT
TGCCCTGGGTCA









113348840
113348855
TGCCCGAACAGG
GTTGACTGGCGG











TCAG (71)
CTAT (72)











37
chr17:
chr17:
CCAAGCTGGTGT
CCAAGCTGGTGT
0
17
4.17
4.19E−04
3′ss
Br.



78188582-
78188564-
GCGCACAGGCCT
GCGCACAGGCAT









78188831
78188831
CTCTTCCCGCCC
CATCGGGAAGAA











AGGC (73)
GCAC (74)











38
chr20:
chr20:
CTCCTTTGGGTT
CTCCTTTGGGTT
0
17
4.17
2.67E−07
3′ss
Br.



45354963-
45354963-
TGGGCCAGGCCC
TGGGCCAGTGAC









45355453
45355502
CAGGTCCCACCA
CTGGCTTGTCCT











CAGC (75)
CAGC (76)











39
chr12:
chr12:
AATATTGCTTTA
AATATTGCTTTA
0
16
4.09
2.79E−07
3′ss
Br.



116413154-
116413118-
CCAAACAGGGAC
CCAAACAGGTCA









116413319
116413319
CCCTTCCCCTTC
CGGAGGAGTAAA











CCCA (77)
GTAT (78)











40
chr14:
chr14:
CAGTTATAAACT
CAGTTATAAACT
0
16
4.09
4.46E−07
3′ss
Br.



71059726-
71059705-
CTAGAGTGAGTT
CTAGAGTGCTTA









71060012
71060012
TATTTTCCTTTT
CTGCAGTGCATG











ACAA (79)
GTAT (80)











41
chr16:
chr16:
GCCTGCCCCGGA
GCCTGCCCCGGA
0
15
4.00
7.77E−06
3′ss
Br.



30012851-
30012851-
AACTCAAGATGT
AACTCAAGATGG









30016688
30016541
TCAGCGATGCAG
CGGTGGGACCCC











GTAG (81)
CCGA (82)











42
chr17:
chr17:
TTCAGGAGGTGG
TTCAGGAGGTGG
0
15
4.00
3.26E−05
3′ss
Br.



57148329-
57148308-
AGCACCAGATAA
AGCACCAGTTGC









57153007
57153007
TTTTTTTCCTCA
GGTCTTGTAGTA











CACA (83)
AGAG (84)











43
chr16:
chr16:
GGATCCTTCACC
GGATCCTTCACC
0
14
3.91
3.01E−07
3′ss
Br.



1402307-
1402307-
CGTGTCTGTCTT
CGTGTCTGGACC









1411686
1411743
TGCAGACAGGTT
CGTGCATCTCTT











CTGT (85)
CCGA (86)











44
chr3:
chr3:
ATTTGGATCCTG
ATTTGGATCCTG
0
14
3.91
8.71E−07
3′ss
Br.



196792335-
196792319-
TGTTCCTCTTTT
TGTTCCTCATAC









196792578
196792578
TTTCTGTTAAAG
AACTAGACCAAA











ATAC (87)
ACGA (88)











45
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
0
13
3.81
1.55E−05
3′ss
Br.



75356052-
75356052-
GGAGAAAGCCTT
GGAGAAAGCTGT









75356580
75356599
TGATTGTCTTTT
TGGAGACACAGT











CAGC (89)
TGCA (90)











46
chr18:
chr18:
AGAAAGAGCATA
AGAAAGAGCATA
0
13
3.81
9.84E−07
3′ss
Br.



33605641-
33573263-
AATTGGAAATAT
AATTGGAAGAGT









33606862
33606862
TGGACATGGGCG
ACAAGCGCAAGC











TATC (91)
TAGC (92)











47
chr1:
chr1:
TCAGCCCTCTGA
TCAGCCCTCTGA
0
13
3.81
6.10E−07
3′ss
Br.



226036315-
226036255-
ACTACAAAGGTG
ACTACAAAACAG









226036597
226036597
TTTGTTCACAGA
AAGAGCCTGCAA











GATC (93)
GTGA (94)











48
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
3
51
3.70
1.35E−09
3′ss
Br.



10723474-
10723474-
TGAGACCGCTTG
TGAGACCGGTGC









10724788
10724802
TTTTCTGCAGGT
AGGCCTGGGGTA











GCAG (95)
GTCT (96)











49
chr2:
chr2:
CAAGTCCATCTC
CAAGTCCATCTC
0
12
3.70
5.71E−03
3′ss
Br.



132288400-
132288400-
TAATTCAGGGTC
TAATTCAGGCAA









132289210
132289236
TGACTTGCAGCC
GGCCAGGCCCCA











AACT (97)
GCCC (98)











50
chr2:
chr2:
CAAGATAGATAT
CAAGATAGATAT
0
12
3.70
4.26E−06
3′ss
Br.



170669034-
170669016-
TATAGCAGGTGG
TATAGCAGAACT









170671986
170671986
CTTTTGTTTTAC
TCGATATGACCT











AGAA (99)
GCCA (100)











51
chr15:
chr15:
GAAACCAACTAA
GAAACCAACTAA
1
24
3.64
4.30E−09
3′ss
Br.



59209219-
59209198-
AGGCAAAGCCCA
AGGCAAAGGTAA









59224554
59224554
TTTTCCTTCTTT
AAAACATGAAGC











CGCA (101)
AGAT (102)











52
chr11:
chr11:
GGGGACAGTGAA
GGGGACAGTGAA
0
11
3.58
5.99E−08
3′ss
Br.



57100545-
57100623-
ATTTGGTGGCAA
ATTTGGTGGGCA









57100908
57100908
GAATGAGGTGAC
GCTGCTTTCCTT











ACTG (103)
TGAC (104)











53
chr1:
chr1:
CTCAGAGCCAGG
CTCAGAGCCAGG
0
11
3.58
3.15E−07
3′ss
Br.



35871069-
35871069-
CTGTAGAGATGT
CTGTAGAGTCCG









35873587
35873608
TTTCTACCTTTC
CTCTATCAAGCT











CACA (105)
GAAG (106)











54
chr2:
chr2:
GAGGAGCCACAC
GAGGAGCCACAC
0
11
3.58
2.22E−07
3′ss
Br.



220044485-
220044485-
TCTGACAGATAC
TCTGACAGTGAG









220044888
220044831
CTGGCTGAGAGC
GGTGCGGGGTCA











TGGC (107)
GGCG (108)











55
chr5:
chr5:
ACTCGCGCCTCT
ACTCGCGCCTCT
0
11
3.58
7.04E−07
3′ss
Br.



150411955-
150411944-
TCCATCTGTTTT
TCCATCTGCCGG









150413168
150413168
GTCGCAGCCGGA
AATACACCTGGC











ATAC (109)
GTCT (110)











56
chrX:
chrX:
ACTTCCTTAGTG
ACTTCCTTAGTG
0
11
3.58
7.37E−07
3′ss
Br.



47059013-
47059013-
GTTTCCAGGTTG
GTTTCCAGGTGG









47059808
47060292
CCAGGGCACTGC
TGGTGCTCACCA











AGCT (111)
ACAC (112)











57
chrX:
chrX:
GTCTTGAGAATT
ACTTCCTTAGTG
0
11
3.58
6.70E−06
5′ss
Br.



47059943-
47059013-
GGAAGCAGGTGG
GTTTCCAGGTGG









47060292
47060292
TGGTGCTCACCA
TGGTGCTCACCA











ACAC (113)
ACAC (112)











58
chr20:
chr20:
TCCAGAGCCCAC
TCCAGAGCCCAC
2
34
3.54
4.87E−09
3′ss
Br.



330007-
330007-
AGTCCCAGCTGC
AGTCCCAGGGGT









330259
330281
ACCTTACCTGCT
CCATGATGCCGA











CCCC (114)
GCTG (115)











59
chr18:
chr18:
CCAAGTTTTGTG
CCAAGTTTTGTG
1
22
3.52
1.96E−05
3′ss
Br.



224200-
224179-
AAAGAAAGTGTA
AAAGAAAGAACA









224923
224923
TGTTTTGTTCAC
TCAGATACCAAA











GACA (116)
CCTA (117)











60
chr11:
chr11:
TCTTCACAGAAC
TCTTCACAGAAC
0
10
3.46
2.99E−08
3′ss
Br.



47195466-
47195391-
ACACTCAAGTGC
ACACTCAACCCC









47196565
47196565
TTGTAGGTCTTG
CTGCCTGGGATG











GTGC (118)
CGCC (119)











61
chr12:
chr12:
GAGAAGCTCACG
TCTTGGAGGAGC
0
10
3.46
4.11E−02
exon
Br.



56604352-
56604352-
ATTACCAGGCAC
CAGTACAGGCAC




incl.




56606779
56607741
CTCATTGTGAAC
CTCATTGTGAAC











ATGC (120)
ATGC (121)











62
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
0
10
3.46
3.25E−08
3′ss
Br.



23237380-
23237380-
TGCTGCATTTTG
TGCTGCATGTAC









23238985
23238999
TATTTTCCAGGT
AGTCTTTGCCCG











ACAG (122)
CTGC (123)











63
chr17:
chr17:
TACTGAAATGTG
TACTGAAATGTG
0
10
3.46
2.49E−05
3′ss
Br.



34942628-
34942628-
ATGAACATATCC
ATGAACATATCC









34943454
34943426
AGGTAATCGAGA
AGAAGCTTGGAA











GACC (124)
GCTG (125)











64
chr1:
chr1:
GAATCTCTTATC
GAATCTCTTATC
0
10
3.46
2.93E−06
3′ss
Br.



145581564-
145581564-
ATTGATGGTTCC
ATTGATGGTTTA









145583935
145583914
TGTTCAGATTGT
TTTATGGAGATT











GATG (126)
CTTA (127)











65
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
1
20
3.39
6.76E−06
3′ss
Br.



869519-
865696-
CTCTCTGGTTTC
CTCTCTGGGGAA









870587
870587
TTTCAGGGCCTG
GGTGAAGAAGGA











CCAT (128)
GCTG (129)











66
chr12:
chr12:
CTTGGAGCTGAC
CTTGGAGCTGAC
7
79
3.32
1.30E−08
3′ss
Br.



107378993-
107379003-
GCCGACGGGGAA
GCCGACGGTTTA









107380746
107380746
CTGACAAGATCA
TTGCAGGGAACT











CATT (130)
GACA (131)











67
chr7:
chr7:
TCCAGCCTGGGC
CTATCAAAAGAG
1
19
3.32
4.35E−08
exon
Br.



8261028-
8261028-
GACAGAAGTCTT
GATATGTTTCTT




incl.




8267267
8268230
GTCTCAAGAAGA
GTCTCAAGAAGA











AAAC (132)
AAAC (133)











68
chr10:
chr10:
TGCGGAGCAAGA
TGCGGAGCAAGA
0
9
3.32
1.37E−04
3′ss
Br.



5497081-
5497081-
GTGGACATCGTT
GTGGACATAAAC









5498027
5498049
TGTTTCCCATTT
TTTACATTTTCC











CTCC (134)
TGTT (135)











69
chr11:
chr11:
AGTCCAGCCCCA
AGTCCAGCCCCA
0
9
3.32
4.66E−07
3′ss
Br.



64900740-
64900723-
GCATGGCACCTC
GCATGGCAGTCC









64900940
64900940
TCCCCACTCCTA
TGTACATCCAGG











GGTC (136)
CCTT (137)











70
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
0
9
3.32
1.49E−09
3′ss
Br.



5595521-
5595508-
AAGAGAGATTTT
AAGAGAGAAGCT









5598803
5598803
GGTAAACAGAGC
CCAAGAGTCAGG











TCCA (138)
ATCG (139)











71
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
9
3.32
8.58E−06
3′ss
Br.



39064137-
39064137-
TGCATTCTCATC
TGCATTCTTTGG









39066874
39066888
TCGCCCACAGTT
ATCGATCAACCC











GGAT (140)
GGGA (141)











72
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
2
28
3.27
2.13E−08
3′ss
Br.



125023777-
125023787-
GCCACGAGACAT
GCCACGAGTATT









125026993
125026993
TGATGGAAGCAG
TCATAGACATTG











AAAC (142)
ATGG (143)











73
chr15:
chr15:
GCCTCACTGAGC
GCCTCACTGAGC
1
18
3.25
5.94E−09
exon
Br.



25207356-
25207356-
AACCAAGAGTAG
AACCAAGAGTGT




incl.




25212175
25213078
TGACTTGTCAGG
CAGTTGTACCCG











AGGA (144)
AGGC (145)











74
ch19:
chr9:
GGGAGATGGATA
GGGAGATGGATA
3
35
3.17
6.19E−08
3′ss
Br.



35813153-
35813142-
CCGACTTGCTCA
CCGACTTGTGAT









35813262
35813262
ATTTCAGTGATC
CAACGATGGGAA











AACG (146)
GCTG (147)











75
chr6:
chr6:
AGGATGTGGCTG
AGGATGTGGCTG
1
17
3.17
5.18E−06
3′ss
Br.



31602334-
31602334-
GCACAGAAGTGT
GCACAGAAATGA









31602574
31602529
CATCAGGTCCCT
GTCAGTCTGACA











GCAG (148)
GTGG (149)











76
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
0
8
3.17
6.00E−04
3′ss
Br.



125442465-
125442465-
TTGCCAGACCTT
TTGCCAGAGGAA









125445146
125445158
TTCTATAGGGAA
TCAAAGACTCCA











TCAA (150)
TCTG (151)











77
chr13:
chr13:
AGCTGAAATTTC
AGCTGAAATTTC
0
8
3.17
1.20E−06
3′ss
Br.



113915073-
113915073-
CAGTAAAGGGGG
CAGTAAAGCCTG









113917776
113917800
GTTTTATTCTTC
GAGATTTGAAAA











TTTT (152)
AGAG (153)











78
chr16:
chr16:
GATGTCACTGTG
GATGTCACTGTG
0
8
3.17
4.76E−02
3′ss
Br.



14966186-
14966186-
ACTATCAAGGGC
ACTATCAAGTCT









14968874
14968892
CGTCTTTCTTCT
TCCATCGACAGT











AGGT (154)
GAAC (155)











79
c11r2:
chr2:
TATCCATTCCTG
TATCCATTCCTG
0
8
3.17
2.22E−07
3′ss
Br.



178096758-
178096736-
AGTTACAGTATA
AGTTACAGTGTC









178097119
178097119
AACTTCCTTCTC
TTAATATTGAAA











ATGC (156)
ATGA (157)











80
chrX:
chrX:
TACAAGAGCTGG
TACAAGAGCTGG
0
8
3.17
2.14E−05
3′ss
Br.



153699660-
153699660-
GTGGAGAGGGTC
GTGGAGAGGTAT









153699819
153699830
CCAACAGGTATT
TATCGAGACATT











ATCG (158)
GCAA (159)











81
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
3
31
3.00
7.42E−06
3′ss
Br.



9728842-
9728855-
GTCCCGTGGGAA
GTCCCGTGGGTT









9730107
9730107
CCAATCTGCCCT
TTTTTCCAGGGA











TTTG (160)
ACCA (161)











82
chr1:
chr1:
AGTTACAACGAA
AGTTACAACGAA
2
23
3.00
8.51E−06
3′ss
Br.



185056772-
185056772-
CACCTCAGTGAC
CACCTCAGGAGG









185060696
185060710
TCTTTTACAGGA
CAATAACAGATG











GGCA (162)
GCTT (163)











83
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
1
15
3.00
3.25E−08
exon
Br.



25212299-
25207356-
ATTTGAAAGTGT
AACCAAGAGTGT




incl.




25213078
25213078
CAGTTGTACCCG
CAGTTGTACCCG











AGGC (164)
AGGC (145)











84
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
7
3.00
1.28E−08
3′ss
Br.



62648919-
62648919-
CCTGGCGGCCCC
CCTGGCGGGTCT









62649352
62649364
CATTTCAGGTCT
GAAGGGGCGTCT











GAAG (165)
CGAT (166)











85
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
0
7
3.00
4.87E−09
3′ss
Br.



64877395-
64877395-
ACGTGCAGTACC
ACGTGCAGGTGG









64877934
64877953
TCTTTTTACCAC
GGCTCCTGTACG











CAGG (167)
AAGA (168)











86
chr19:
chr19:
CTATGGGCTCAC
CTATGGGCTCAC
0
7
3.00
1.24E−03
3′ss
Br.



41084118-
41084118-
TCCTCTGGTCCT
TCCTCTGGTTCG









41084353
41084367
CCTGTTGCAGTT
TCGCCTGCAGCT











CGTC (169)
TCGA (170)











87
chr1:
chr1:
TATCTCTGGGAA
TATCTCTGGGAA
0
7
3.00
3.66E−06
3′ss
Br.



35917392-
35917377-
AAAACACATTTC
AAAACACAGGGA









35919157
35919157
TTTTTTTGCAGG
CCTGATGGGGTG











GGAC (171)
CAGC (172)











88
chr22:
chr22:
TCATCCAGAGCC
TCATCCAGAGCC
0
7
3.00
1.95E−06
3′ss
Br.



50966161-
50966146-
CAGAGCAGGGGA
CAGAGCAGATGC









50966940
50966940
TGTCTGACCAGA
AAGTGCTGCTGG











TGCA (173)
ACCA (174)











89
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
0
7
3.00
8.14E−08
3′ss
Br.



139837449-
139837395-
CTGTGAAGGCCC
CTGTGAAGATCT









139837800
139837800
CCGCCCCGCGAC
GGAGCAACGACC











CTGG (175)
TGAC (176)











90
chr1:
chr1:
CCCGAGCTCAGA
CCCGAGCTCAGA
4
38
2.96
2.79E−08
3′ss
Br.



3548881-
3548902-
GAGTAAATTCTC
GAGTAAATATGA









3549961
3549961
CTTACAGACACT
GATCGCCTCTGT











GAAA (177)
CCCA (178)











91
chr19:
chr19:
GTGCTTGGAGCC
GTGCTTGGAGCC
3
29
2.91
3.56E−07
3′ss
Br.



55776746-
55776757-
CTGTGCAGACTT
CTGTGCAGCCTG









55777253
55777253
TCCGCAGGGTGT
GTGACAGACTTT











GCGC (179)
CCGC (180)











92
chr1:
chr1:
GCTGGACACGCT
GCTGGACACGCT
1
14
2.91
2.38E−07
exon
Br.



39332671-
39333282-
GACCAAGGCATC
GACCAAGGTGTT




skip




39338689
39338689
ACTTAGGAGCTG
GGTAGCCTTATA











CTAC (181)
TGAA (182)











93
chr2:
chr2:
CCCCTGAGATGA
CCCCTGAGATGA
1
14
2.91
1.82E−07
exon
Br.



27260570-
27260570-
AGAAAGAGCTCC
AGAAAGAGCTCC




incl.




27260682
27261013
CTGTTGACAGCT
TGAGCAGCCTGA











GCCT (183)
CTGA (184)











94
chr2:
chr2:
CTGAACTTTGGG
CTGAACTTTGGG
3
28
2.86
7.09E−06
3′ss
Br.



233599948-
233599948-
CCTGAATGATGT
CCTGAATGGCTC









233600472
233612324
GTTTGGACCCCG
CGAGCTCTGTCC











AATA (185)
AGTG (186)











95
chr11:
chr11:
AGATCGCCTGGC
AGATCGCCTGGC
0
6
2.81
4.87E−09
3′ss
Br.



3697619-
3697606-
TCAGTCAGTTTT
TCAGTCAGACAT









3697738
3697738
TCTCTCTAGACA
GGCCAAACGTGT











TGGC (187)
AGCC (188)











96
chr11:
chr11:
GGAGGTGGACCT
GGAGGTGGACCT
0
6
2.81
1.25E−06
3′ss
Br.



68363686-
68363686-
GAGTGAACAATT
GAGTGAACCACC









68367788
68367808
TCTCCCCTCTTT
CAACTGGTCAGC











TTAG (189)
TAAC (190)











97
chr12:
chr12:
TACAGATGGTAA
TACAGATGGTAA
0
6
2.81
8.19E−07
3′ss
Br.



72315234-
72315234-
AATGCAAGTTTG
AATGCAAGGAAT









72316743
72316762
ATTTTTCATATC
TGCCACAAGCAG











CAGG (191)
TCTG (192)











98
chr16:
chr16:
CCCTGCTCATCA
CCCTGCTCATCA
0
6
2.81
5.11E−07
3′ss
Br.



685022-
684956-
CCTACGGGTCTG
CCTACGGGCCCT









685280
685280
TCCCAGGCTCTC
ATGCCATCAATG











TGGG (193)
GGAA (194)











99
chr1:
chr1:
GGCTCCCATTCT
GGCTCCCATTCT
0
6
2.81
3.43E−04
3′ss
Br.



155630724-
155630704-
GGTTAAAGAGTG
GGTTAAAGGCCA









155631097
155631097
TTCTCATTTCCA
GTCTGCCATCCA











ATAG (195)
TCCA (196)











100
chr1:
chr1:
CTGCACTTATAA
CTGCACTTATAA
0
6
2.81
L.50E−06
3′ss
Br.



47108988-
47108973-
ATATTCAGTGTT
ATATTCAGACCC









47110832
47110832
CCACCTTGCAGA
GAGGGGAAGCTG











CCCG (197)
CAGC (198)











101
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
6
2.81
1.29E−02
3′ss
Br.



36627480-
36627512-
GAACCCAGTATT
GAACCCAGAGAG









36629198
36629198
TCCAGGACCAAG
CAGTATCTTTAT











TGAG (199)
TGAG (200)











102
chr6:
chr6:
CCCTAGTCTGAT
AGAGAAGTCGTT
0
6
2.81
6.01E−04
5′ss
Br.



31919565-
31919381-
TCCTTTAGGTTG
TCATTCAAGTTG









31919651
31919651
GTGTAATCAGCT
GTGTAATCAGCT











GGGG (201)
GGGG (52)











103
chr1:
chr1:
TTCCCCATCAAC
TTCCCCATCAAC
3
26
2.75
6.26E−07
3′ss
Br.



19480448-
19480433-
ATCAAAAGTTTT
ATCAAAAGTTCC









19481411
19481411
GTTGTCTGCAGT
AATGGTGGCAGT











TCCA (202)
AAGA (203)











104
chr11:
chr11:
CCAGCTGCATTG
CCAGCTGCATTG
4
32
2.72
6.93E−04
3′ss
Br.



67161081-
67161081-
CAAGTTCGGACT
CAAGTTCGGGGT









67161193
67161161
GTGAGTCCCTGC
GCGGAAGACTCA











AGGC (204)
CAAC (205)











105
chr12:
chr12:
GGCCAGCCCCCT
GGCCAGCCCCCT
6
41
2.58
1.26E−09
3′ss
Br.



120934019-
120934019-
TCTCCACGGCCT
TCTCCACGGTAA









120934204
120934218
TGCCCACTAGGT
CCATGTGCGACC











AACC (206)
GAAA (207)











106
chr14:
chr14:
CGCTCTCCGCCT
AGGGAGACGTTC
2
17
2.58
1.96E−05
exon
Br.



75348719-
75349327-
TCCAGAAGGGGT
CCTGCCTGGGGT




skip




75352288
75352288
CTCCTTATGCCA
CTCCTTATGCCA











GGGA (208)
GGGA (209)











107
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
11
2.58
1.14E−07
3′ss
Br.



23398690-
23398690-
CCCCCAAGTCCT
CCCCCAAGTGAT









23399766
23399784
TTGTTCTTTTGC
GTATATCTCTCA











AGTG (210)
TCAA (211)











108
chr11:
chr11:
CTACGGCGGTGC
CTACGGCGGTGC
0
5
2.58
1.09E−07
3′ss
Br.



44957237-
44957213-
CCTCCTCACCCC
CCTCCTCAGCAT









44958353
44958353
CTTTTCATCCCC
CTCCCTGATCAT











CGCC (212)
GTGG (213)











109
chr12:
chr12:
CCTGGTCGCAGT
CCTGGTCGCAGT
0
5
2.58
9.89E−04
exon
Br.



57494682-
57493873-
TCAACAAGATGA
TCAACAAGGAGA




incl.




57496072
57496072
GGAATCTGATGC
TCCTGCTGGGCC











TCAG (214)
GTGG (215)











110
chr16:
chr16:
CACCAAGCAGAG
CACCAAGCAGAG
0
5
2.58
1.04E−07
3′ss
Br.



15129410-
15129410-
GCTTCCAGTCTG
GCTTCCAGGCCA









15129852
15129872
TCTGCCCTTTCT
GAAGCCTTTTAA











GTAG (216)
AAGG (217)











111
chr17:
chr17:
GGGACTCCCCCA
GGGACTCCCCCA
0
5
2.58
9.75E−05
3′ss
Br.



41164294-
41164294-
AAGACAAGCTTT
AAGACAAGGTCC









41164946
41165063
TCTTTCAGTAAA
CATTTTCAGTGC











TGTA (218)
CCAA (219)











112
chr17:
chr17:
GCACTGCTGTTC
GCACTGCTGTTC
0
5
2.58
1.25E−05
3′ss
Br.



61511981-
61511955-
AACCTCGGCTTC
AACCTCGGGGGC









61512446
61512446
TCCCTTCCTCTC
AAGTATAGCGCA











ACCC (220)
TTTG (221)











113
chr19:
chr19:
ACGAGACCATTG
ACGAGACCATTG
0
5
2.58
1.71E−05
3′ss
Br.



2247021-
2247021-
CCTTCAAGGAGC
CCTTCAAGGTGC









2247564
2247592
CCTCTCTGTCCC
CGAGCAGAGAGA











CCGC (222)
TCGA (223)











114
chr21:
chr21:
AAGATGTCCCTG
AAGATGTCCCTG
0
5
2.58
5.11E−07
3′ss
Br.



38570326-
38570326-
TGAGGATTGTGT
TGAGGATTGCAC









38572514
38572532
GTTTGTTTCCAC
TGGGTGCAAGTT











AGGC (224)
CCTG (225)











115
chr6:
chr6:
AGAGAAGTCGTT
AGAGAAGTCGTT
0
5
2.58
2.67E−07
3′ss
Br.



31919381-
31919381-
TCATTCAATCTG
TCATTCAAGTTG









31919551
31919651
ATTCCTTTAGGT
GTGTAATCAGCT











CAGC (226)
GGGG (52)











116
chrX:
chrX:
AGCCCAGCAGTT
AGCCCAGCAGTT
0
5
2.58
5.15E−07
3′ss
Br.



48751114-
48751100-
CCGAAATGTCTC
CCGAAATGCGCC









48751182
48751182
CCTTCTCCAGCG
CCCATTCCTGGA











CCCC (227)
GGAC (228)











117
chr17:
chr17:
CCCTCCCCCGGC
ACCCAAGCCTTG
2
16
2.5
3.35E−04
exon
Br.



40714505-
40714237-
TCCTGTCGGCCT
AGGTTTCAGCCT




inc1.




40714629
40714629
GGGCAGCATGGC
GGGCAGCATGGC











CGTA (229)
CGTA (18)











118
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
1
10
2.46
1.54E−06
3′ss
Br.



25213229-
25213229-
AAAACCAGCCTT
AAAACCAGGCTC









25219533
25219457
CCCCTAGGTCTT
CATCTACTCTTT











CAGA (230)
GAAG (231)











119
chr2:
chr2:
CAAGTCCATCTC
CAAGTCCATCTC
2
15
2.42
6.24E−03
3′ss
Br.



132288400-
132288400-
TAATTCAGCCAA
TAATTCAGGCAA









132289224
132289236
CTCTCAAGGCAA
GGCCAGGCCCCA











GGCC (232)
GCCC (98)











120
chr7:
chr7:
CTATCAAAAGAG
CTATCAAAAGAG
2
15
2.42
9.00E−05
exon
Br.



8267481-
8261028-
GATATGTTCATT
GATATGTTTCTT




inc1.




8268230
8268230
TTAGGAGGCCAA
GTCTCAAGAAGA











GGCA (233)
AAAC (133)











121
chr3:
chr3:
GTCTTCCAATGG
GTCTTCCAATGG
7
41
2.39
2.38E−07
3′ss
Br.



148759467-
148759455-
CCCCTCAGCCTT
CCCCTCAGGAAA









148759952
148759952
TTCTCTAGGAAA
TGATACACCTGA











TGAT (234)
AGAA (235)











122
chr8:
chr8:
GCACCTCCCCGG
GCACCTCCCCGG
4
25
2.38
3.96E−02
exon
Br.



144873910-
144873610-
GACGCCTGCCCT
GACGCCTGTCAC




inc1.




144874045
144874045
TGTCTGGAAAGA
CGGACTTTGCTG











AGTT (236)
AGGA (237)











123
chr17:
chr17:
TGGACCCCAGAC
GTCCCGGAACCA
1
9
2.32
5.71E−03
exon
Br.



3828735-
3828735-
CACACCGGAAGA
CATGCACGAAGA




inc1.




3831533
3831956
AATGAGCCAGAA
AATGAGCCAGAA











GTGA (238)
GTGA (239)








124
chr11:
chr11:
TCTGTGTTCCCA
TGTATGACGTCA
0
4
2.32
2.08E−03
5′ss
Br.



66040546-
66039931-
TCGCACAGGAAT
CTGACCAGGAAT









66043274
66043274
CCTACGCCAACG
CCTACGCCAACG











TGAA (240)
TGAA (241)











125
chr12:
chr12:
GGAATATGATCC
GGAATATGATCC
0
4
2.32
6.10E−04
3′ss
Br.



15272132-
15264351-
CACCCTCGTACT
CACCCTCGAATC









15273996
15273996
TCTCAAAGAGGA
AACCTACCGACA











TGGC (242)
CCAA (243)











126
chr16:
chr16:
GAACTGGCACCG
GAACTGGCACCG
0
4
2.32
1.02E−06
3′ss
Br.



313774-
313774-
ACAGACAGTGTC
ACAGACAGATCC









313996
314014
CCCTCCCTCCCC
TGTTTCTGGACC











AGAT (244)
TTGG (245)











127
chr19:
chr19:
TGATGAAGACCT
TGATGAAGACCT
0
4
2.32
L.48E−03
3′ss
Br.



44116292-
44112259-
TTCCCCAGATCT
TTCCCCAGGCCC









44118380
44118380
CTTAGGTGAAGA
CGAGCATTCCTC











CATG (246)
TGAT (247)











128
chr1:
chr1:
CCAGGCCGACAT
CCAGGCCGACAT
0
4
2.32
4.27E−07
3′ss
Br.



228335400-
228335400-
GGAGAGCAGCCC
GGAGAGCAGCAA









228336058
228336071
CACCCACAGGCA
GGAGCCCGGCCT











AGGA (248)
GTTT (249)











129
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
4
2.32
5.15E−07
3′ss
Br.



34144042-
34144042-
ACGGAGAGTTCT
ACGGAGAGGTAC









34144761
34144743
CTGTGACCAGAC
TGAGGACAAATC











ATGA (250)
AGTT (50)











130
chr2:
chr2:
TTCGTCCATATG
TTCGTCCATATG
0
4
2.32
2.38E−03
3′ss
Br.



198267783-
198267759-
TGCATAAGCTTC
TGCATAAGATCC









198268308
198268308
TTCTCTTTTCTC
TCGTGGTCATTG











TTTT (251)
AACC (252)











131
chr3:
chr3:
AGGGATGGCCAG
AGAAGGGAGCGA
0
4
2.32
8.01E−04
5′ss
Br.



47969840-
47969840-
TGGTAGTGGGTC
TACTACAGGGTC









47981988
48019354
TCCAACTGAATT
TCCAACTGAATT











CCTT (253)
CCTT (254)











132
chr4:
chr4:
CCAATGTGGTTC
CCAATGTGGTTC
0
4
2.32
1.00E−05
3′ss
Br.



38907482-
38907482-
AAAACACATTAT
AAAACACAGGTA









38910197
38910212
CTCATCTGCAGG
AAAGTGTCTTAA











GTAA (255)
CTGG (256)











133
ch17:
chr7:
CCATTGATGCAA
CCATTGATGCAA
0
4
2.32
7.45E−03
exon
Br.



94227316-
94218044-
ACGCAGCAATGG
ACGCAGCAGAAC




incl.




94228086
94228086
AGTTTCGCTCCT
TTGCCACATCAG











GTTG (257)
ACTC (258)











134
chr8:
chr8:
GCTGCATCTGGA
CAGTGTTAGTGA
0
4
2.32
6.84E−03
5′ss
Br.



17873340-
17872349-
GGTCCTGGGAAG
ATGACTATGAAG









17882869
17882869
CAGAATCTGGTA
CAGAATCTGGTA











ATAT (259)
ATAT (260)











135
chr17:
chr17:
ACAAGGACACAG
ACAAGGACACAG
10
53
2.30
5.76E−06
3′ss
Br.



73518592-
73518292-
AAAACAAGCCTT
AAAACAAGCTGG









73519333
73519333
CCCACACAGGCC
AGCACCGCTGCA











CTGC (261)
CCTC (262)











136
chr16:
chr16:
AGCTCGGACCAA
AGCTCGGACCAA
9
48
2.29
1.29E−03
3′ss
Br.



47495337-
47495337-
GCGCTCAGTTTT
GCGCTCAGCTTA









47497792
47497809
AAAATTGCTATA
GCCTGCGACGCT











GCTT (263)
TATG (264)











137
chr6:
chr6:
AGGGGGCTCTTT
AGGGGGCTCTTT
6
32
2.24
3.39E−03
3′ss
Br.



91269953-
91269933-
ATATAATGTTTG
ATATAATGTGCT









91271340
91271340
TGCCTTTCTTTC
GCATGGTGCTGA











GCAG (265)
ACCA (266)











138
chr15:
chr15:
GCCCCCAACTGA
GCCCCCAACTGA
2
13
2.22
4.76E−03
exon
Br.



41130464-
41128480-
GAAGCTGGGCTG
GAAGCTGGTGCC




incl.




41130740
41130740
GAGTGCTGTGGC
CTTGGTGTGGTG











ACAA (267)
GAAG (268)











139
chr17:
chr17:
GAACGAGATCTC
AGTATCAGAAGG
4
21
2.14
6.40E−03
5′ss
Br.



2276080-
2275782-
ATCCCACTAACT
ACAAAAAGAACT









2276246
2276246
ACAAAGAGCTGG
ACAAAGAGCTGG











AGCT (269)
AGCT (270)











140
chr17:
chr17:
TGAAGGTCCAGG
TGAAGGTCCAGG
8
35
2.00
4.45E−02
3′ss
Br.



4885470-
4885455-
GCATGGAGCCTG
GCATGGAGTGTC









4886051
4886051
TCTCCTGGCAGT
TCTATGGCTGCT











GTCT(271)
ACGT(272)











141
chr16:
chr16:
GGCGGCCGCGCC
GGCGGCCGCGCC
2
11
2.00
3.29E−02
exon
Br.



1728357-
1728357-
GGCTCCAGGAAA
GGCTCCAGGGCC




incl.




1733509
1735439
TGGCAACTGCTG
ATGAAGCCCCCA











ACAG(273)
GGAG(274)











142
chr11:
chr11:
CCTTCCAGCTAC
CCTTCCAGCTAC
1
7
2.00
1.25E−04
3′ss
Br.



2993509-
2993473-
ATCGAAACGCAT
ATCGAAACTTTA









2997253
2997253
GAGGATGTTGTA
CCTAAAGCAGTA











TTTC(275)
AAAA(276)











143
chr10:
chr10:
CTTTTCTCTTCT
GATGTGATGAAC
0
3
2.00
2.72E−03
5′ss
Br.



69583150-
69583150-
TTTTATAGGTTG
TATCTTCGGTTG









69595149
69597691
AACAAATCCTGG
AACAAATCCTGG











CAGA(277)
CAGA(278)











144
chr11:
chr11:
GCACTGGGCATT
GCACTGGGCATT
0
3
2.00
1.28E−07
3′ss
Br.



66053068-
66053007-
CAGAAAAGTCTC
CAGAAAAGGTTC









66053171
66053171
TCTTCCTCACCC
TCCCCGGAGGTG











CTGC(279)
CTGG(280)











145
chr11:
chr11:
CTGTCACAGGGG
CTGTCACAGGGG
0
3
2.00
2.18E−03
3′ss
Br.



77090454-
77090433-
AGTTTACGTCTT
AGTTTACGGGAA









77090938
77090938
GCATGTCTCTCT
TGCCAGAGCAGT











TACA(281)
GGGC(282)











146
chr12:
chr12:
GGGTGCAAAAGA
GGGTGCAAAAGA
0
3
2.00
2.66E−07
3′ss
Br.



57032980-
57033091-
TCCTGCAGCCAT
TCCTGCAGGACT









57033763
57033763
TCCAGGTTGCTG
ACAAATCCCTCC











AGGT(283)
AGGA(284)











147
chr12:
chr12:
GGCACCCCAAAA
GGCACCCCAAAA
0
3
2.00
9.82E−07
3′ss
Br.



58109976-
58109976-
GATGGCAGATCA
GATGGCAGGTGC









58110164
58110194
GTCTCTCCCTGT
GAGCCCGACCAA











TCTC(285)
GGAT(286)











148
chr17:
chr17:
GCATCTCAGCCC
GCATCTCAGCCC
0
3
2.00
2.72E−07
3′ss
Br.



16344444-
16344444-
AAGAGAAGTTTC
AAGAGAAGGTTA









16344670
16344681
TTTGCAGGTTAT
TATTCCCAGAGG











ATTC(287)
ATGT(288)











149
chr1:
chr1:
CTTGCCTTCCCA
CTTGCCTTCCCA
0
3
2.00
2.32E−04
3′ss
Br.



154246074-
154246074-
TCCTCCTGCAAA
TCCTCCTGAACT









154246225
154246249
CACCTGCCACCT
TCCAGGTCCTGA











TTCT(289)
GTCA(290)











150
chr1:
chr1:
CTACACAGAGCT
CTACACAGAGCT
0
3
2.00
8.14E−08
3′ss
Br.



32096333-
32096443-
GCAGCAAGGTGT
GCAGCAAGCTCT









32098095
32098095
GCACCCAGCTGC
GTCCCAAATGGG











AGGT(291)
CTAC(292)











151
chr2:
chr2:
ACCTGTTACCAC
ACCTGTTACCAC
0
3
2.00
1.17E−04
3′ss
Br.



101622533-
101622533-
TTTCAAAATTTC
TTTCAAAAATCT









101635459
101622811
TGTGCTAAACAG
ACAGACAGTCAA











TGTT(293)
TGTG(294)











152
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
3
2.00
3.82E−06
3′ss
Br.



26437445-
26437430-
GGTGGAAACATT
GGTGGAAAAATT









26437921
26437921
TTATTTTACAGA
GACAGCGTATGC











ATTG(295)
CATG(296)











153
chr3:
chr3:
CAACGAGAACAA
CAACGAGAACAA
0
3
2.00
2.29E−07
3′ss
Br.



101401353-
101401336-
GCTATCAGTTAC
GCTATCAGGGCT









101401614
101401614
TTTTACCCCACA
GCTAAGGAAGCA











GGGC(297)
AAAA(298)











154
chr5:
chr5:
TCTATATCCCCT
TCTATATCCCCT
0
3
2.00
1.27E−06
3′ss
Br.



177576859-
177576839-
CTAAGACGCACT
CTAAGACGGACC









177577888
177577888
TCTTTCCCCTCT
TGGGTGCAGCCG











GTAG (299)
CAGG (300)











155
chr6:
chr6:
TGGAGCCAGTTA
TGGAGCCAGTTA
0
3
2.00
9.28E−04
3′ss
Br.



31506716-
31506632-
CTGGGCAGGTGT
CTGGGCAGGTGT









31506923
31506923
GTTTTTGTGACA
CTGTACTGGTGA











GTCA (301)
TGTG (302)











156
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
13
54
1.97
1.08E−05
3′ss
Br.



129771378-
129771384-
GGAATCAGTATC
GGAATCAGCCTT









129790554
129790554
ACAGGCAGAAGC
AGTATCACAGGC











TCTG (303)
AGAA (304)











157
chrX:
chrX:
CAGCACTAGGTT
CAGCACTAGGTT
7
30
1.95
8.04E−04
exon
Br.



135758876-
135760115-
ATAAAGAGGAGT
ATAAAGAGAGGA




skip




135761693
135761693
CTAGTAAAAGCC
TGTCTTATATCT











CTAA (305)
TAAA (306)











158
chr6:
chr6:
GCCCCCGTTTTC
GCCCCCGTTTTC
4
18
1.93
9.28E−05
3′ss
Br.



31936315-
31936315-
CTGCCCAGCCCT
CTGCCCAGTACC









31936399
31936462
TGTCCTCAGTGC
TGAAGCTGCGGG











ACCC (307)
AGCG (308)











159
chr2:
chr2:
GCCGCCGCCGCC
CACCTTATGAAG
10
40
1.90
4.22E−03
5′ss
Br.



97757449-
97757449-
GCCGCCAGGCTC
TATAGCAGGCTC









97760437
97757599
TGATGCTGGTGT
TGATGCTGGTGT











CTGG (309)
CTGG (310)











160
chr19:
chr19:
AGTGGCAGTGGC
AGTGGCAGTGGC
6
25
1.89
2.97E−03
3′ss
Br.



6731065-
6731122-
TGTACCAGCCCA
TGTACCAGCTCT









6731209
6731209
CAGGAAACAACC
TGGTGGAGGGCT











CGTA (311)
CCAC (312)











161
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
4
16
1.77
5.02E−05
3′ss
Br.



54954250-
54954322-
ATAAGGAGTTCT
ATAAGGAGGTAA









54957496
54957496
CTTGTAGGATGC
AACCTGTTTAGA











CACT (313)
AATT (314)











162
chr2:
chr2:
CCAAGAGACAGC
CCCCTGAGATGA
4
16
1.77
3.39E−06
exon
Br.



27260760-
27260570-
ACATTCAGCTCC
AGAAAGAGCTCC




incl.




27261013
27261013
TGAGCAGCCTGA
TGAGCAGCCTGA











CTGA (315)
CTGA (184)











163
chr10:
chr10:
TCAGAGCAGTCG
CTACGACAGTGA
10
35
1.71
1.55E−02
5′ss
Br.



75290593-
75290593-
GGACACAGGACA
AGATTCAGGACA









75294357
75296026
CCTGACTGATAG
CCTGACTGATAG











TGAA (316)
TGAA (317)











164
chr1:
chr1:
CTGTTGTGTCCG
CTGTTGTGTCCG
19
63
1.68
5.06E−05
3′ss
Br.



155278867-
155278867-
TTTTGAAGAGCC
TTTTGAAGAATG









155279833
155279854
CTTTGCTCCTCC
AACGGAGACCAG











CTCA (318)
AATT (319)











165
chr16:
chr16:
CCGGCCCTACAG
CCCTCCGCCTCC
6
21
1.65
3.26E−02
exon
Br.



630972-
632309-
GCTGGCGGATAA
TGATGCAGATAA




skip




632882
632882
ACCCACTGCCCT
ACCCACTGCCCT











ACAG (320)
ACAG (321)











166
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
18
57
1.61
6.30E−07
3′ss
Br.



54954239-
54954322-
ATAAGGAGGATG
ATAAGGAGGTAA









54957496
54957496
CCACTGGAAATG
AACCTGTTTAGA











TTGA (322)
AATT (314)











167
chr14:
chr14:
TGAAAAGTCCAG
TCCTGGAGGAGC
15
47
1.58
1.41E−02
5′ss
Br.



39734625-
39736726-
AGGAAGAGGTTG
TACGCAGGGTTG









39746137
39746137
TGGCAGCACTGC
TGGCAGCACTGC











CTGA (323)
CTGA (324)











168
chr13:
chr13:
GTCATGGCAGAA
CTATAGCTACTG
10
32
1.58
1.25E−02
exon
Br.



21157158-
21164006-
GACCTCCATCCA
GATATGGGTCCA




skip




21165105
21165105
AGACATCTCTGG
AGACATCTCTGG











CATC (325)
CATC (326)











169
chr17:
chr17:
CCGGAGCCCCTT
CCGGAGCCCCTT
5
17
1.58
4.45E−02
3′ss
Br.



45229302-
45229284-
CAAAAAAGACTT
CAAAAAAGTCTG









45232037
45232037
TTCGTGTTTTAC
TTGCCAGAATCG











AGTC (327)
GCCA (328)











170
chr16:
chr16:
CCACAGATACTA
CCACAGATACTA
3
11
1.58
1.99E−02
3′ss
Br.



47484364-
47462809-
TTAGGAGGCCAT
TTAGGAGGGAAT









47485306
47485306
ACCACCCTGAAC
TTATCATGGCAT











GCGC (329)
CCAG (330)











171
chr12:
chr12:
TGTTCAAGTTCC
CCTGGTCGCAGT
1
5
1.58
1.50E−04
exon
Br.



57493873-
57493873-
CAAAGCAGGAGA
TCAACAAGGAGA




incl.




57494628
57496072
TCCTGCTGGGCC
TCCTGCTGGGCC











GTGG (331)
GTGG (215)











172
chr16:
chr16:
ACTCCCAGCTCA
ACTCCCAGCTCA
0
2
1.58
6.10E−05
3′ss
Br.



56403209-
56403239-
ATGCAATGGTTC
ATGCAATGGCTC









56419830
56419830
CATACCATCTGG
ATCAGATTCAAG











TACT (332)
AGAT (333)











173
chr17:
chr17:
ATCACTGTGACT
ATCACTGTGACT
0
2
1.58
4.98E−05
3′ss
Br.



80013701-
80013701-
TCCCTGAGGTCT
TCCCTGAGCTGC









80013861
80013876
CTGCTCCTCAGC
TGTCCCCCAGCA











TGCT (334)
ACGT (335)











174
chr18:
chr18:
ATCCTCTCAATC
ATCCTCTCAATC
0
2
1.58
4.76E−02
3′ss
Br.



51729496-
51715381-
AAAATAAGTTTG
AAAATAAGGGTA









51731367
51731367
TGTGCACTTTTC
AACCAGACTTGA











TGCT (336)
ATAC (337)








175
chr1:
chr1:
CTATTCCTTTAT
CTATTCCTTTAT
0
2
1.58
5.34E−04
3′ss
Br.



145109684-
145109684-
TGAATTTGTTTT
TGAATTTGATAC









145112354
145112372
CTTCATCATTCT
TTTCATTCAGAA











AGAT (338)
AACC (339)











176
chr2:
chr2:
AGTCATACCTGG
AGTCATACCTGG
0
2
1.58
3.46E−03
3′ss
Br.



242274627-
242274627-
AGCAGCAGTTTG
AGCAGCAGAAAA









242275373
242275389
TTTCTTTTCTAG
AATTGAAAGAAC











AAAA (340)
TGTC (341)











177
chr3:
chr3:
GCAACCAGTTTG
GCAACCAGTTTG
0
2
1.58
1.37E−04
3′ss
Br.



49395199-
493951S0-
GGCATCAGCTGC
GGCATCAGGAGA









49395459
49395459
CCTTCTCTCCTG
ACGCCAAGAACG











TAGG (342)
AAGA (343)











178
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
2
1.58
3.60E−05
3′ss
Br.



152022314-
152022314-
AATGGCAGCACC
AATGGCAGACAA









152024139
152024022
AACAGGTCCGCC
TGATTGAAGCTC











AAAT (344)
ACGT (345)











179
chr5:
chr5:
GCCTGATGCCCG
GCCTGATGCCCG
0
2
1.58
1.29E−02
exon
Br.



1323984-
1324928-
AATTTCAGGCCA
AATTTCAGTTTG




skip




1325865
1325865
TGAAGTACTTGT
GCACTTACAGCG











CATA (346)
AATC (347)











180
chr5:
chr5:
AGATTGAAGCTA
AGATTGAAGCTA
0
2
1.58
6.18E−06
3′ss
Br.



132439718-
132439718-
AAATTAAGTTTT
AAATTAAGGAGC









132439902
132439924
CTGTCTTACCCA
TGACAAGTACTT











TTCC (348)
GTAG (349)











181
chr5:
chr5:
AGCACAAGCTAT
AGCACAAGCTAT
0
2
1.58
5.76E−06
3′ss
Br.



44813384-
44813384-
GTATCAAGCATA
GTATCAAGGATT









44814996
44815014
ACTTTCTTCTAC
CTGGAGTGAAGC











AGGA (350)
AGAT (351)











182
chr6:
chr6:
AGATGTAAAAGT
AGATGTAAAAGT
0
2
1.58
5.43E−04
3′ss
Br.



52546712-
52546712-
GTCACTGTTTTG
GTCACTGTTTAC









52548863
52548875
GTTTTCAGTTAC
AGCTTTCTTCCT











AGCT (352)
GGCT (353)











183
chr7:
chr7:
CTGCAGCCTCCG
CCATTGATGCAA
0
2
1.58
8.78E−03
exon
Br.



94218044-
94218044-
CCTCCCAGGAAC
ACGCAGCAGAAC




incl.




94227241
94228086
TTGCCACATCAG
TTGCCACATCAG











ACTC (354)
ACTC (258)











184
chr15:
chr15:
AGGATGATGCAG
AGGATGATGCAG
10
28
1.4
1.70E−03
3′ss
Br.



59373483-
59373483-
CATCCAACTGGT
CATCCAACGCGG









59376300
59376327
CTTTTTGTGTTC
GCACATGAACGC











TGTG (355)
CCCC (356)











185
chr1:
chr1:
TGGTGAAATGGA
TGGTGAAATGGA
12
33
1.39
1.25E−03
3′ss
Br.



153925126-
153925111-
CCCCAAAGTCTT
CCCCAAAGTACC









153925280
153925280
TCTCTTTCAAGT
TGCTATTGAGGA











ACCT (357)
GAAC (358)











186
chr1:
chr1:
AGCTTAAAGAAC
GATCAAGGCAAC
9
25
1.38
3.31E−02
exon
Br.



151739775-
151740709-
TGTATTCGTTTG
CGGGAAAGTTTG




skip




151742647
151742647
ACTGCAACCCTG
ACTGCAACCCTG











GAGT (359)
GAGT (360)











187
chr19:
chr19:
AACACACCAACT
AACACACCAACT
1
4
1.32
8.52E−04
3′ss
Br.



47342877-
47342835-
TTGTGGAGGTCC
TTGTGGAGTTCC









47349249
47349249
TGGCAATCTCCG
GGAACTTTAAGA











TTGC (361)
TCAT (362)











188
chr15:
chr15:
GCGGGTCTGCAG
GTTCCAGGTCCT
5
13
1.22
5.55E−04
exon
Br.



75631685-
75632219-
CCTACGCAAACT
CCTGGCAGAACT




skip




75632305
75632305
GAAGCAGGCCCA
GAAGCAGGCCCA











GACC (363)
GACC (364)











189
chr1:
chr1:
CCCGCTGCCCCA
ATTCTGATATAG
5
13
1.22
1.52E−02
exon
Br.



212459633-
212502673-
GCTCAAAGATCA
TAAAAATGATCA




skip




212506838
212506838
GTGCTAACATCT
GTGCTAACATCT











TCCG (365)
TCCG (366)











190
chr22:
chr22:
ATGAGTTTCCCA
ATGAGTTTCCCA
2
6
1.22
1.59E−03
3′ss
Br.



30976673-
30976688-
CCGATGGGGAGG
CCGATGGGGAGA









30976998
30976998
AAGACCGCAGGA
TGTCAGCGCAGG











AGGA (367)
AGGA (368)











191
chr7:
chr7:
AGTTTATTTAAC
AGTTTATTTAAC
2
6
1.22
3.40E−02
exon
Br.



80535232-
80458061-
ATTTGATGAGCC
ATTTGATGAACT




incl.




80545994
80545994
TACCTTGTACAA
TCGAGAAACCAA











TGCT (369)
GACC (370)











192
chr8:
chr8:
CCACCTAGCAGC
CCACCTAGCAGC
2
6
1.22
1.17E−03
intron
Br.



145153766-
145153691-
CACCAGAGACCA
CACCAGAGGTTA




reten-




145153768
145153768
GAGGTGGCACAG
CAAGGGGAGAGT




tion






GCAG (371)
GGCC (372)











193
chr9:
chr9:
TCCAGGATCCTG
GGCAGCGGAGGG
2
6
1.22
8.61E−03
exon
Br.



96285645-
96278551-
AGGCATGGCCAT
GCGACAAACCAT




incl.




96289436
96289436
ATCAGCGGGAAC
ATCAGCGGGAAC











AAGA (373)
AAGA (374)











194
chr2:
chr2:
GGCAACTTCGTT
GGCAACTTCGTT
20
47
1.19
5.26E−03
3′ss
Br.



106781255-
106781240-
AATATGAGCTTT
AATATGAGGTCT









106782511
106782511
CTACTCAACAGG
ATCCAGGAAAAT











TCTA (375)
GGTG (376)











195
chr19:
chr19:
GGAGCCTGGGCA
GGAGCCTGGGCA
6
15
1.19
1.98E−02
3′ss
Br.



7976215-
7976215-
TCTCGTTGCCCT
TCTCGTTGGTGG









7976299
7976320
GCCCGTCTCCCT
AGCTGGCAACAG











CCCA (377)
GACA (378)











196
chr11:
chr11:
CTGGTGTGCTTG
CTGGTGTGCTTG
3
8
1.17
4.87E−02
exon
Br.



9161795-
9161401-
GGAGCCAGGGTT
GGAGCCAGAGAT




incl.




9163486
9163486
ATCATGAAGATT
CACCTCCTACAC











AAAT (379)
CACT (380)











197
chr1:
chr1:
ATTGGAGGAGCT
ATTGGAGGAGCT
10
23
1.13
3.12E−03
exon
Br.



160252899-
160253429-
TCTGGAAAGATG
TCTGGAAAGTGC




skip




160254844
160254844
CCCTCTTCGCTT
TCTTGATGATTT











CCCA (381)
CGAT (382)











198
chr19:
chr19:
AATGACGTGCTG
AATGACGTGCTG
7
16
1.09
1.69E−02
3′ss
Br.



16641724-
16641691-
CACCACTGGGCC
CACCACTGCCAG









16643408
16643408
CTGACGCGCGGA
CGCAAGCAGGCC











AAGT (383)
CGGG (384)











199
chr3:
chr3:
GCCTGGGGTGGA
GCCTGGGGTGGA
9
20
1.07
3.01E−02
exon
Br.



39141945-
39141994-
GAGGGCAGCCCC
GAGGGCAGTCTG




skip




39142237
39142237
CCAGCTACCACA
GGATGTGGCATT











AGAA (385)
GGCT (386)











200
chr2:
chr2:
GGAAATGGGACA
GGAAATGGGACA
11
24
1.06
3.05E−03
3′ss
Br.



230657846-
230657861-
GGAGGCAGAGGA
GGAGGCAGCTTT









230659894
230659894
TCACAGGCTTTA
TCTCTCAACAGA











AAAT (387)
GGAT (388)











201
chr10:
chr10:
AGACCGACTGCC
AGACCGACTGCC
5
11
1.00
2.09E−02
exon
Br.



123718925-
123719110-
AGTAATAGGAGA
AGTAATAGAGCC




skip




123719872
123719872
TTGTGAAGACCT
TGTTAGTATTAA











TTGA (389)
TGAA (390)











202
chr1:
chr1:
TCATGCTAGCCG
TCATGCTAGCCG
5
11
1.00
3.31E−02
exon
Br.



44064584-
44064584-
AGGCCCAGTGGC
AGGCCCAGGAAA




incl.




44067741
44069086
GGCCAGAGGAGT
CCACTATCAGCG











CCGA (391)
GCCT (392)











203
chr1:
chr1:
GAAGGCAGCTGA
GAAGGCAGCTGA
4
9
1.00
1.37E−03
3′ss
Br.



11131045-
11131030-
GCAAACAGTTCT
GCAAACAGCTGC









11132143
11132143
CTCCCTTGCAGC
CCGGGAACAGGC











TGCC (393)
AAAG (394)











204
ch16:
chr6:
GCCAACAGCCAA
GCCAACAGCCAA
3
7
1.00
6.32E−03
exon
Br.



109690220-
109691670-
TTCTACAGGTAC
TTCTACAGCTAA




skip




109697276
109697276
AACAAATAACAC
ACCCACAGTTCA











TGTG (395)
GCCC (396)











205
chr17:
chr17:
CCCATCAACTGC
CCCATCAACTGC
2
5
1.00
4.46E−02
exon
Br.



37873733-
37873733-
ACCCACTCCCCT
ACCCACTCCTGT




skip




37879571
37876039
CTGACGTCCATC
GTGGACCTGGAT











ATCT (397)
GACA (398)











206
chr17:
chr17:
GCGGAAAGAATT
GCGGAAAGAATT
2
5
1.00
4.49E−02
3′ss
Br.



5250220-
5250220-
GCATGAAGAGCG
GCATGAAGTTTG









5253766
5253745
ACAACAACACAA
CCATCTCTTGGA











CCAG (399)
GCAA (400)











207
chr1:
chr1:
TGTGGGAATTAC
AAGAAGGGATGG
2
5
1.00
7.58E−03
exon
Br.



27260910-
27250657-
AATTCAAGCTTA
CAGAGAAGCTTA




incl.




27267947
27267947
TCACACAGACTT
TCACACAGACTT











TCAG (401)
TCAG (402)











208
chr5:
chr5:
CTTCCTCAAGTC
CTTCCTCAAGTC
1
3
1.00
1.35E−02
3′ss
Br.



176759270-
176759247-
GCCCAAAGCTCC
GCCCAAAGACAA









176761284
176761284
CCCGTTTCTTCT
CGTGGACGACCC











CCCC (403)
CACG (404)











209
chr7:
chr7:
TCTTCGCTGGTG
TCTTCGCTGGTG
1
3
1.00
8.43E−03
exon
Br.



44619227-
44620838-
GCAAACTGTATC
GCAAACTGCGGG




skip




44621047
44621047
GTGAAGAGCGCT
TGCATCTCGACA











TCCG (405)
TCCA (406)











210
chr1:
chr1:
GCAAGAAGTACA
GCAAGAAGTACA
0
1
1.00
9.69E−03
3′ss
Br.



165619201-
165619201-
AAGTGGAGTATG
AAGTGGAGTATC









165620230
165620250
TGCTTTGTTGTG
CTATCATGTACA











ACAG (407)
GCAC (408)











211
chr3:
chr3:
TGTAGGAGCAAT
TGTAGGAGCAAT
0
1
1.00
2.54E−04
3′ss
Br.



42826828-
42826812-
GACTGTTGCATT
GACTGTTGGTAT









42827519
42827519
CTTTTTCTTTAG
GGGCTATTCCAT











GTAT (409)
GTAT (410)











212
chr8:
chr8:
CCTTCCTGGATC
AAGTGCAGATAG
0
1
1.00
5.33E−04
exon
Br.



117738411-
117738411-
CCCCTAAGGTGG
ATGGCCTTGTGG




incl.




117746515
117767904
TATTAAAGATAA
TATTAAAGATAA











TCAA (411)
TCAA (412)











213
chrX:
chrX:
CAGGTCTAACTC
CAGGTCTAACTC
0
1
1.00
1.53E−02
3′ss
Br.



54835809-
54835809-
GCTTCCAGGCCC
GCTTCCAGGCTG









54836550
54836154
CAGCAGATGAAC
AAGCTTCAGAAA











CTGA (413)
AGGA (414)











214
chr!6:
chr16:
CCTCCCCATACC
GCCTGCCCCGGA
10
20
0.93
3.40E−02
exon
Br.



30012361-
30012851-
TGAGCTCGATGG
AACTCAAGATGG




skip




30016541
30016541
CGGTGGGACCCC
CGGTGGGACCCC











CCGA (415)
CCGA (82)











215
chr6:
c1u6:
GCAAAAGGATAT
GCAAAAGGATAT
10
20
0.93
2.78E−02
3′ss
Br.



43006222-
43006210-
ACCAGGAGCATT
ACCAGGAGGGGT









43006303
43006303
TATTTCAGGGGT
CCTCAAGATTCG











CCTC (416)
AGAT (417)











216
chr6:
chr6:
CACTCCAATTTA
CACTCCAATTTA
9
18
0.93
1.40E−02
exon
Br.



135517140-
135517140-
TAGATTCTGATT
TAGATTCTTTCT




incl.




135518098
135520045
CTTCATCATGGT
TAAACACTTCCA











GTGA (418)
GTAA (419)











217
chr7:
chr7:
TGAGAGTCTTCA
TGAGAGTCTTCA
45
85
0.90
3.07E−04
3′ss
Br.



99943591-
99943591-
GTTACTAGTTTG
GTTACTAGAGGC









99947339
99947421
TCTTTCCTAGAT
GGATTTCCCTGA











CCAG (420)
CTGA (421)











218
chr12:
chr12:
TTAACAGCATTT
CCCAGTCATTCA
10
19
0.86
1.21E−02
intron
Br.



111085013-
111082934-
TGTTTTGCGATT
ACAGGAAGGATT




reten-




111085015
111085015
CCTGCCAGCTCC
CCTGCCAGCTCC




tion






CAGG (422)
CAGG (423)











219
chr4:
chr4:
GATGAATGCTGA
GATGAATGCTGA
4
8
0.85
2.40E−02
exon
Br.



141300346-
141300346-
CATGGATGATCT
CATGGATGCAGT




skip




141302115
141300722
CTCTGCAAGAGT
TGATGCTGAAAA











AGAT (424)
TCAA (425)











220
chr10:
chr10:
GTCAATGCTTCC
GTCAATGCTTCC
18
33
0.84
3.71E−02
3′ss
Br.



114905856-
114905856-
ATGTCCAGCTTT
ATGTCCAGGTTC









114910741
114910756
CTGTCTTCTAGG
CCTCCCCATATG











TTCC (426)
GTCC (427)











221
chr16:
chr16:
TATGGCAAGGAG
TATGGCAAGGAG
7
13
0.81
2.25E−02
3′ss
Br.



30767593-
30767593-
GTCGACCTTCTC
GTCGACCTCTGG









30767675
30767687
TTTCCCAGCTGG
GCCTGTGGGGTG











GCCT (428)
ATCT (429)











222
chr3:
chr3:
TGGTTTTACCTC
TGGTTTTACCTC
7
13
0.81
5.98E−03
3′ss
Br.



128890351-
128890381-
GGATAGAGACAT
GGATAGAGGTTT









128890476
128890476
TTGTTATCGCTG
CCAGTTTGTTTC











TGGT (430)
CTCG (431)











223
chr1:
chr1:
GAATCCGTATCT
GAATCCGTATCT
34
60
0.80
2.74E−04
3′ss
Br.



155278756-
155278756-
GGGAACAGAGCC
GGGAACAGAATG









155279833
155279854
CTTTGCTCCTCC
AACGGAGACCAG











CTCA (432)
AATT (433)











224
chr20:
chr20:
TCCAGGAGTTCC
TTTGACTAGGGT
22
39
0.80
1.59E−02
exon
Br.



264722-
264722-
AGGTTCCGTGTT
CCAACCAGTGTT




skip




270899
270199
TCACTTCAAGCC
TCACTTCAAGCC











CACT (434)
CACT (435)











225
chr1:
chr1:
GGGCCTGATGAA
GGGCCTGATGAA
30
52
0.77
2.84E−03
exon
Br.



53370762-
53372283-
TGACATCGCTTC
TGACATCGCAGC




skip




53373539
53373539
CTCGGCAGTCAT
CTTCCCTGCACC











GGGA (436)
CACC (437)











226
chr4:
chr4:
AGCCCCAGGATG
AGCCCCAGGATG
16
28
0.77
1.45E−02
exon
Br.



5815889-
5815889-
CCTCGCAGCTCT
CCTCGCAGACGT




skip




5825343
5819937
CGGAAGAACTGG
GCCTTCTGCCAT











TTGT (438)
GATT (439)











227
chr20:
chr20:
ACTTGCCTGTGA
ACTTGCCTGTGA
15
26
0.75
1.83E−03
3′ss
Br.



47741142-
47741124-
ATTTCGAGTCTT
ATTTCGAGGTGG









47752369
47752369
TCCCTCTGAAAC
CCCGGGAGAGTG











AGGT (440)
GCCC (441)











228
chrX:
chrX:
TACCCGGGACAA
TACCCGGGACAA
2
4
0.74
4.57E−02
3′ss
Br.



48933637-
48933604-
CCCCAAGGCCGC
CCCCAAGGGGCT









48934088
48934088
CCACCCCACCCC
CTGTGACCTCTG











CCAT (442)
CCCC (443)











229
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
39
64
0.70
4.20E−07
3′ss
Br.



67890660-
67890642-
GATAGATCTTCT
GATAGATCTGGC









67890765
67890765
TTTTCACATTAC
CTGAAGCACGAG











AGTG (444)
GACA (445)











230
chr1:
chr1:
GCTGTACCTTCA
GCTGTACCTTCA
18
29
0.66
2.84E−03
3′ss
Br.



156705701-
156705701-
GGAACAGGCCCT
GGAACAGGGTTT









156706410
156706423
TTCTCCCAGGTT
CCATGCTGAGCT











TCCA (446)
CCTG (447)











231
chr10:
chr10:
TAAAGCGACTCA
TAAAGCGACTCA
29
46
0.65
1.78E−02
exon
Br.



101507147-
101507147-
TTGAGCAGGAGG
TTGAGCAGGCAA




skip




101514285
101510125
TGGTATAACAGA
AAGGCAGGATTG











CAGA (448)
TGGT (449)











232
chr12:
chr12:
TGGGAATCTGGC
TGGGAATCTGGC
31
49
0.64
3.09E−04
3′ss
Br.



117595889-
117595868-
CAGAGAAGTCTT
CAGAGAAGGTGC









117603289
117603289
TCTGTCTTGTTT
TTGACATCCTCC











TGAA (450)
AGCA (451)











233
chr2:
chr2:
AGAAAACATCGA
AGAAAACATCGA
8
13
0.64
2.66E−02
exon
Br.



114472772-
114475427-
ATTCAGAGCTTG
ATTCAGAGAGTT




skip




114476730
114476730
ATAATGGAACTA
CCAGAAGACAGC











TACA (452)
GAAC (453)











234
chr1I:
chr11:
CGTCCGCCAGTC
AGCCGGGCGTTG
34
53
0.63
1.78E−02
5′ss
Br.



504996-
504996-
GTCCCGAGGCAT
GGGGAAAGGCAT









507112
506608
GAAGAACTCTTG
GAAGAACTCTTG











ACTG (454)
ACTG (455)











235
chrX:
chrX:
ACTAATCTTCAG
CAAACACCTCTT
14
22
0.62
2.22E−04
exon
Br.



123224814-
123224614-
CATGCCATTCGG
GATTATAATCGG




incl.




123227867
123227867
CGTGGCACAAGC
CGTGGCACAAGC











CTAA (456)
CTAA (457)











236
chr9:
chr9:
CACCACAAAATC
CACCACAAAATC
37
57
0.61
6.00E−04
3′ss
Br.



140622981-
140622981-
ACAGACAGCTTG
ACAGACAGCAGC









140637822
140637843
CTTGCCTTTTGT
TGCAGTATCTCG











TTTA (458)
GAAG (459)











237
chr2:
chr2:
CTCCTACTACAC
AGAGCTCAAAGA
34
52
0.60
2.66E−02
exon
Br.



152324660-
152325065-
AATCTAAGATTT
AGTGTTTAATTT




skip




152325154
152325154
CAGAAATGGCCA
CAGAAATGGCCA











AAGA (460)
AAGA (461)











238
chr12:
chr12:
ATTTCCAGAGGA
ATTTCCAGAGGA
49
74
0.58
1.10E−04
3′ss
Br.



95660408-
95660408-
TTTACACTTTTG
TTTACACTGGTC









95663814
95663826
CTTGACAGGGTC
AGTGCTGCTTGC











AGTG (462)
CCAT (463)











239
chr7:
chr7:
GAGTCGGCGCCG
CACAGAGAGCTG
5
8
0.58
4.45E−02
exon
Br.



44880611-
44880611-
AGAACATGTTTC
GGCTACAGTTTC




skip




44887567
44882875
CTGTGGGCCGCA
CTGTGGGCCGCA











TCCA (464)
TCCA (465)











240
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
46
68
0.55
4.09E−04
3′ss
Br.



75554088-
75554088-
TGCTCCAGTGGT
TGCTCCAGGTTC









75554298
75554313
TTCTCCCACAGG
CCGGCCCCCAAG











TTCC (466)
TCGC (467)











241
chrX:
chrX:
CAAACACCTCTT
CAAACACCTCTT
14
21
0.55
2.21E−02
exon
Br.



123224614-
123224614-
GATTATAACACG
GATTATAATCGG




incl.




123224703
123227867
CAGGTAACATGG
CGTGGCACAAGC











ATGT (468)
CTAA (457)











242
chr2:
chr2:
TACTCCAGCTTC
TACTCCAGCTTC
30
44
0.54
8.18E−03
3′ss
Br.



86398468-
86398435-
AGCAACAGCACC
AGCAACAGCAGG









86400772
86400772
TACAGAAGCGGC
TGATACCCTGTC











TCAA (469)
GGTC (470)











243
chr17:
chr17:
TCTCAGCTGACG
GGCATGCAACCA
13
19
0.51
4.21E−03
exon
Br.



47882807-
47886570-
AATGCAAGGCAC
GGCACCAGGCAC




skip




47888837
47888837
CAACGGAGAGAC
CAACGGAGAGAC











AGCT (471)
AGCT (472)











244
chr1:
chr1:
TCAAATCATTTA
TCAAATCATTTA
9
13
0.49
3.77E−02
3′ss
Br.



109743522-
109743522-
CCTCCAAGCAGC
CCTCCAAGAGGA









109745534
109745565
CAGCTCCTGTCA
CTCCTGATGGAT











CCAT (473)
TTGA (474)











245
chr11:
chr11:
AGCAAAAAGGGG
AGCAAAAAGGGG
35
49
0.47
2.40E−02
3′ss
Br.



502249-
502181-
TGTCTCAGAATC
TGTCTCAGGCCA









504823
504823
TCCGGCCTGTGA
CTCTTCACCTCC











AACT (475)
ACCA (476)











246
chr6:
chr6:
TGTTGCCTCCGC
TGGTCATGGCCA
44
60
0.44
5.91E−04
exon
Br.



31611971-
31611971-
GGCCGCAGGACA
AACCCTGGGACA




incl.




31612083
31612301
GCAGGTGCCAGG
GCAGGTGCCAGG











CTTC (477)
CTTC (478)











247
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
63
84
0.41
4.16E−05
3′ss
Br.



30310151-
30310133-
ATTTGAATCTCT
ATTTGAATAATC









30310420
30310420
TTCTCTCCCTTC
TTATCTTGGCTT











AGAA (479)
TGGA (480)











248
chr6:
chr6:
TGGTCATGGCCA
TGGTCATGGCCA
51
68
0.41
4.27E−03
exon
Br.



31612191-
31611971-
AACCCTGGGCTC
AACCCTGGGACA




incl.




31612301
31612301
CACCCTCATCCA
GCAGGTGCCAGG











GCTG (481)
CTTC (478)











249
chr10:
chr10:
TGCAGATTCCAA
CCTTCCACCCAA
49
63
0.36
4.56E−02
exon
Br.



34649187-
34649187-
AAGAAACGAAAG
GGGAACTGAAAG




incl.




34661425
34663801
CAGAAGATGAGG
CAGAAGATGAGG











ATAT (482)
ATAT (483)











250
chr4:
chr4:
AGGAGGGCCCCC
AGGAGGGCCCCC
43
54
0.32
1.35E−02
3′ss
Br.



860289-
860322-
TGCCGCTGGCAA
TGCCGCTGCTGA









860743
860743
CAACTCCCAGCC
CCCCTTTGGCCC











CTGC (484)
GCTT (485)











251
chr8:
chr8:
AACAACTGCCCA
AACAACTGCCCA
3
4
0.32
4.44E−02
3′ss
Br.



99054946-
99055003-
GCTTTGAGTGGC
GCTTTGAGGAAA









99057170
99057170
AATAATATTGAA
TCTGAAATAGAG











CTGG (486)
TACT (487)











252
chr8:
chr8:
GTTGTGCCCATG
GTTGTGCCCATG
66
81
0.29
4.37E−02
exon
Br.



48694815-
48691654-
ACCTCCAGGTTA
ACCTCCAGTGAT




incl.




48694938
48694938
GGATTAATTGAG
CCCAGGGCACCG











TGGC (488)
CCGT (489)











253
chr20:
chr20:
GTTAATGGGTTT
GTTAATGGGTTT
57
68
0.25
2.24E−02
exon
Br.



57470739-
57470739-
AATGGAGAGGGC
AATGGAGATGAG




incl.




57473995
57478585
GGCGAAGAGGAC
AAGGCAACCAAA











CCGC (490)
GTGC (491)











254
chr20:
chr20:
GCAAGGAGCAAC
GTTAATGGGTTT
59
69
0.22
4.34E−03
exon
Br.



57474040-
57470739-
AGCGATGGTGAG
AATGGAGATGAG




incl.




57478585
57478585
AAGGCAACCAAA
AAGGCAACCAAA











GTGC (492)
GTGC (491)











255
chr19:
chr19:
AGTTTGAGATGA
AGTTTGAGATGA
79
91
0.2
2.28E−02
exon
Br.



17339118-
17339118-
AGCGAATGGATC
AGCGAATGCTCC




incl.




17339611
17339817
CTGGCTTCCTGG
CCCTACCAGGGG











ACAA (493)
TCGC (494)











256
chrX:
chrX:
AGAAACCTTGAA
AGAAACCTTGAA
84
95
0.18
4.29E−02
exon
Br.



2209644-
2310515-
CGACAAAGTGGA
CGACAAAGAGAC




skip




2326785
2326785
ATTTTTATACTG
GTGAGTCTTGCT











TGAC (495)
GTGT (496)











257
chrY:
chrY:
AGAAACCTTGAA
AGAAACCTTGAA
84
95
0.18
4.29E−02
exon
Br.



2159644-
2260515-
CGACAAAGTGGA
CGACAAAGAGAC




skip




2276785
2276785
ATTTTTATACTG
GTGAGTCTTGCT











TGAC (495)
GTGT (496)











258
chr11:
chr11:
ACCCCTTTGGCA
ACCCCTTTGGCA
0
60
5.93
5.12E−05
3′ss
CLL



67815439-
67815439-
TCGATCCTGCCC
TCGATCCTATTT









67815553
67816345
TTTCCTCAGCAC
GGAGCCTGGCTG











AAGA (497)
CCAA (498)











259
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
59
5.91
7.08E−07
3′ss
CLL



97285513-
97285499-
GTCAACAGAGTT
GTCAACAGGACT









97297048
97297048
TCCCTTATAGGA
GGCTGGACAATG











CTGG (9)
GCCC (10)











260
chr10:
chr10:
TAAAGTGTTGGC
TAAAGTGTTGGC
0
51
5.7
5.10E−07
3′ss
CLL



93244412-
93244412-
TTTACTTAAATT
TTTACTTAATAC









93244921
93244936
TATCTTTACAGA
TGCAAACAATTT











TACT (499)
AGTT (500)











261
chr21:
chr21:
ACCTCGTCAGAA
ACCTCGTCAGAA
0
48
5.61
2.38E−05
3′ss
CLL



47970657-
47970657-
ACAACCAGAGTT
ACAACCAGAGGT









47971529
47971546
CCCCCGTTTCTA
TGGACCAGCCTC











GAGG (501)
AATG (502)











262
chr22:
chr22:
TCATCCAGAGCC
TCATCCAGAGCC
0
48
5.61
3.58E−03
3′ss
CLL



50966161-
50966146-
CAGAGCAGGGGA
CAGAGCAGATGC









50966940
50966940
TGTCTGACCAGA
AAGTGCTGCTGG











TGCA (173)
ACCA (174)











263
chr13:
chr13:
AAAGATTTCAGA
AAAGATTTCAGA
0
39
5.32
1.50E−02
3′ss
CLL



26970491-
26970491-
AGAAATACTATT
AGAAATACGTAT









26971275
26971289
TCTCTTTCAGGT
ACCAACTGCAGC











ATAC (503)
CTTA (504)











264
chr5:
chr5:
CCAAAAGAGGGG
CTCCATGCTCAG
0
39
5.32
4.28E−05
exon
CLL



865696-
865696-
ATAATGAGGGAA
CTCTCTGGGGAA




incl.




869359
870587
GGTGAAGAAGGA
GGTGAAGAAGGA











GCTG (505)
GCTG (129)











265
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
38
5.29
4.92E−04
3′ss
CLL



39064137-
39064137-
TGCATTCTCATC
TGCATTCTTTGG









39066874
39066888
TCGCCCACAGTT
ATCGATCAACCC











GGAT (140)
GGGA (141)











266
chr10:
chr10:
TCATCTTGAAAA
TCATCTTGAAAA
0
34
5.13
3.62E−05
3′ss
CLL



89519557-
89516679-
ATGAAAATTCCT
ATGAAAATGTGG









89527429
89527429
ATTTTACAGCTG
ATAGGCATGTAG











AGGA (506)
ACCT (507)











267
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
34
5.13
3.01E−05
3′ss
CLL



35282126-
35282104-
GGGCTACATCCC
GGGCTACATACC









35284762
35284762
CTTGGTTCTCTG
ATCTGCCAGCAT











TTAC (35)
GACT (36)











268
chr10:
chr10:
ACCCTGTCTACC
ACCCTGTCTACC
1
64
5.02
4.28E−05
3′ss
CLL



102276734-
102276717-
AGCCTGTGTTTT
AGCCTGTGGATA









102286155
102286155
CTGCCACCTACA
GACCATGAAGCT











GGAT (508)
GAAG (509)











269
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
1
62
4.98
8.04E−09
3′ss
CLL



75356052-
75356052-
GGAGAAAGCCTT
GGAGAAAGCTGT









75356580
75356599
TGATTGTCTTTT
TGGAGACACAGT











CAGC (89)
TGCA (90)











270
chr19:
chr19:
TGACACAGCCCT
TGACACAGCCCT
1
59
4.91
4.19E−04
3′ss
CLL



16264018-
16264018-
GCAGGCAGGGTC
GCAGGCAGAAGG









16265147
16265208
CGTGCAGGACCT
ATCCCGCAAACG











TTCC (510)
TGGA (511)











271
chr7:
chr7:
GCGGGGCGAGGG
GCGGGGCGAGGG
1
59
4.91
8.04E−09
3′ss
CLL



102074108-
10207410S-
CAGCTCCGCGTT
CAGCTCCGGGAA









102076648
102076671
TCTCTGAATTCT
GGAACGTCCCAG











CCCC (512)
GGAT (513)











272
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
29
4.91
3.49E−03
3′ss
CLL



1014583J0-
101458296-
CTAATCAATTTT
CTAATCAAGGGA









101460665
101460665
CTGCCTATAGGG
AGGAAGATCTAT











GAAG (25)
GAAC (26)











273
ch17:
chr7:
CCACCTCACCAT
CCACCTCACCAT
0
29
4.91
1.26E−02
3′ss
CLL



99954506-
99954506-
CACCCAGGGCAG
CACCCAGGCCCT









99955849
99955842
CCCCTCCACAGG
CAGGCAGCCCCT











GCCC (514)
CCAC (515)











274
chr19:
chr19:
GATGGTGGATGA
GATGGTGGATGA
1
57
4.86
7.10E−04
3′ss
CLL



23545541-
23545527-
ACCCACAGTTTT
ACCCACAGGTAT









23556543
23556543
TTTTTTTCAGGT
ATGTCCTCATTT











ATAT (11)
TCCT (12)











275
chr3:
chr3:
GCCAACCTAGAG
GCCAACCTAGAG
1
56
4.83
2.18E−05
3′ss
CLL



108403188-
108403188-
CCCCCCTGCTCT
CCCCCCTGATGA









108405274
108405291
CTGCCTCTTACA
CTGGCATAGCCT











GATG (516)
GGGC (517)











276
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
27
4.81
1.14E−04
3′ss
CLL



71198039-
71198039-
TTGTGAAATCAT
TTGTGAAAGTTT









71199162
71199138
TACTTCTAGATG
TGATTCATGGAT











ATGC (31)
TCAC (32)











277
chr6:
chr6:
AACCGGGGGAGC
AACCGGGGGAGC
0
27
4.81
8.95E−03
3′ss
CLL



41040823-
41040823-
GAGGCACGTTTC
GAGGCACGGAGT









41046743
41046767
TTTCCCCACCTT
GTACCTCACAGC











TCTA (518)
CTTC (519)











278
chr11:
chr11:
CACACAGACTGC
CACACAGACTGC
1
54
4.78
3.38E−06
3′ss
CLL



62376298-
62376277-
GTTCGATGAGTG
GTTCGATGCCTT









62376433
62376433
TCTTCCCCCTGC
GCTGTTCACCCT











CTTA (520)
GATG (521)











279
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
26
4.75
9.14E−07
3′ss
CLL



74358911-
74358911-
AACCAGAGTGTT
AACCAGAGCTCC









74360478
74360499
GTCTTTTCTCCC
TGGTACAGTTTG











CCCA (61)
TTCA (62)











280
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
2
79
4.74
1.89E−06
3′ss
CLL



4104212-
4104212-
ACAGCTAATTCT
ACAGCTAAGCAA









4104471
4104492
CTTTCCTCTGTC
GCACTGAGCGAG











TTCA (69)
GTGA (70)











281
chr17:
chr17:
AGACCTACCAGA
AGACCTACCAGA
0
25
4.70
1.18E−02
3′ss
CLL



62574712-
62574694-
AGGCTATGTGTT
AGGCTATGAACA









62576906
62576906
TATTAATTTTAC
GAGGACAACGCA











AGAA (39)
ACAA (40)











282
ch17:
chr7:
gtttttacctct
GTTTTTACCTCT
1
49
4.64
1.80E−08
3′ss
CLL



76943820-
76943806-
GCCTCCTGATCT
GCCTCCTGGTTT









76950041
76950041
CTCATCCTAGGT
TCATACTCTGCA











TTTC (522)
CACC (523)











283
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
24
4.64
3.30E−05
3′ss
CLL



62701988-
62701988-
ACACACAGCCCT
ACACACAGGTGC









62703210
62703222
GTTCACAGGTGC
AGACCCGCAGCT











AGAC (29)
CTGA (30)











284
chr3:
chr3:
CACTGCTGGGAG
CACTGCTGGGAG
0
24
4.64
1.42E−07
3′ss
CLL



129284872-
129284860-
AGTGGAAGTTGC
AGTGGAAGATTC









129285369
129285369
TTCCACAGATTC
CTGAGAGCTGCC











CTGA (524)
GGCC (525)











285
chr11:
chr11:
GATTTTGGAGAG
GATTTTGGAGAG
0
23
4.58
1.27E−04
3′ss
CLL



33080641-
33080641-
GCAACCAACTTT
GCAACCAAATTC









33083060
33083075
GTTTTTCACAGA
CCTGGACTTTGT











TTCC (526)
CACC (527)











286
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
23
4.58
1.48E−03
3′ss
CLL



179835004-
179834989-
TAAACGAGTTTT
TAAACGAGGTAT









179846373
179846373
ATCATTTACAGG
GTGACGCATTCC











TATG (53)
CAGA (54)











287
chr2:
chr2:
TGCAGAACTGGA
TGCAGAACTGGA
0
23
4.58
2.35E−02
3′ss
CLL



23977668-
23977644-
TAAAGAAGTGTA
TAAAGAAGGTGC









23980287
23980287
TTTTTTTGTCTC
TTCTAAAGTAAA











AATT (528)
GAAA (529)











288
chr5:
chr5:
ACTCTTATGCAG
ACTCTTATGCAG
0
23
4.58
4.37E−03
3′ss
CLL



1579622-
1581810-
TCCCCATGAGGT
TCCCCATGAGGA









1585098
1585098
TATGCTTATGTT
GATCCTAGTCTC











TCTC (530)
ACCA (531)











289
chr6:
chr6:
AGTGTTTTACCA
AGTGTTTTACCA
0
23
4.58
2.41E−04
3′ss
CLL



30884736-
30884736-
TGGATGTTGTCA
TGGATGTTGGCT









30884871
30884881
TTCCAGGGCTCC
CCTCAGTGGCTG











TCAG (532)
TGAC (533)











290
chr6:
chr6:
TTTATGATGCTG
TTTATGATGCTG
0
23
4.58
1.66E−02
3′ss
CLL



49416664-
49416640-
CTTTAAAGTTTT
CTTTAAAGCTCA









49419178
49419178
GTTAATGTTTTT
TTAATGAAATTG











CTTT (534)
AAGA (535)











291
chr8:
chr8:
ATCTAAAAACAG
ATCTAAAAACAG
0
23
4.58
3.15E−03
3′ss
CLL



61741365-
61741365-
AAGAGCAGGTCC
AAGAGCAGGTGC









61742868
61742880
TTTTTTAGGTGC
AAAAACTTCAAG











AAAA (536)
CTAT (537)











292
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
2
68
4.52
3.76E−08
3′ss
CLL



109102364-
109102364-
TCTATAAAATTT
TCTATAAAATAC









109102954
109102966
ACCCCCAGATAC
AGCTGGCTGAAA











AGCT (1)
TAAC (2)











293
chr15:
chr15:
GGATTGCAGCCA
GGATTGCAGCCA
0
22
4.52
5.30E−05
3′ss
CLL



72859518-
72859518-
ACACAAAGTTTC
ACACAAAGGAAT









72862504
72862517
TCTTCATAGGAA
GTCCCAAATGCC











TGTC (538)
ATGT (539)











294
chr5:
chr5:
GGTTTCGAGTTT
GGTTTCGAGTTT
0
22
4.52
1.57E−02
3′ss
CLL



109181707-
109181707-
GAATAGTGTTTT
GAATAGTGGTCA









109183328
109183357
GCTTGTTTGTTT
GATTGAAGTTAT











GTTT (540)
CATG (541)











295
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
22
4.52
5.36E−04
3′ss
CLL



125759640-
125759640-
TCCTAAAGCCTC
TCCTAAAGATAA









125760854
125760875
TCTCTTTCTTTG
AGTCCTGTTTAT











TTTA (67)
GACC (68)











296
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
2
65
4.46
7.66E−06
3′ss
CLL



71939542-
71939542-
TGCCTCAGTCAC
TGCCTCAGATGG









71939690
71939770
TTTACAGCTGCA
GGAGGATGAGAA











TCGT (47)
GCCC (48)











297
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
2
65
4.46
2.31E−08
3′ss
CLL



64877395-
64877395-
ACGTGCAGTACC
ACGTGCAGGTGG









64877934
64877953
TCTTTTTACCAC
GGCTCCTGTACG











CAGG (167)
AAGA (168)











298
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
21
4.46
1.50E−04
3′ss
CLL



14031735-
14031735-
TCACCAAGCCTC
TCACCAAGGTGC









14034130
14034145
GTCCTCCCCAGG
CGCCTGCCCCTG











TGCC (59)
TCAA (60)











299
chr11:
chr11:
CGCAAGTACTTC
CGCAAGTACTTC
0
20
4.39
2.24E−03
3′ss
CLL



64676597-
64676622-
CTGCCCCATCCA
CTGCCCCAGGTA









64676742
64676742
GCAGCACACAGT
GTGGTGACTGTG











GGGA (542)
AACC (543)











300
chr22:
chr22:
TTCATAACAAAC
TCATCAATGCCC
0
20
4.39
1.08E−04
5′ss
CLL



24210086-
24204389-
CAGTAAATCACA
CGACCTTGCACA









24210667
24210667
TTCAGGAATTCA
TTCAGGAATTCA











CCAA (544)
CCAA (545)











301
chr2:
chr2:
AAATTTAACATT
AAATTTAACATT
0
20
4.39
2.96E−02
3′ss
CLL



24207701-
24207701-
ACTCATAGTTTT
ACTCATAGAGTA









24222524
24222541
TGCTGTTTTACA
AGCCATATCAAA











GAGT (546)
GACT (547)











302
chr11:
chr11:
CACCGGGAGCTG
CACCGGGAGCTG
2
59
4.32
8.17E−07
3′ss
CLL



64119858-
64119858-
CAGGGCCGCCCC
CAGGGCCGGCAC









64120198
64120215
TTGTCCATCCCA
GAGCAGCTGCAG











GGCA (548)
GCCC (549)











303
chr11:
chr11:
GGAGGTGGACCT
GGAGGTGGACCT
0
19
4.32
5.52E−04
3′ss
CLL



68363686-
68363686-
GAGTGAACAATT
GAGTGAACCACC









68367788
68367808
TCTCCCCTCTTT
CAACTGGTCAGC











TTAG (189)
TAAC (190)











304
chr11:
chr11:
ATTGGACACAGA
CTGTCTCTAGGC
0
19
4.32
5.03E−04
5′ss
CLL



984190-
981299-
GATGGGATATCG
TAAGCAGAATCG









984644
984644
TGACGTCTGCAT
TGACGTCTGCAT











CCAC (550)
CCAC (551)











305
chr17:
chr17:
GGGACCTCACCA
GGGACCTCACCA
0
19
4.32
5.14E−03
3′ss
CLL



43522984-
43523029-
AGCGCCCGCCCC
AGCGCCCGATCT









43527983
43527983
TCATCAACCTGC
GCAGGCAGGCCC











AGAT (552)
TGAA (553)











306
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
2
57
4.27
1.96E−04
3′ss
CLL



139837449-
139837395-
CTGTGAAGGCCC
CTGTGAAGATCT









139837800
139837800
CCGCCCCGCGAC
GGAGCAACGACC











CTGG (175)
TGAC (176)











307
chr4:
chr4:
GAGTGTGAATCA
GAGTGTGAATCA
2
56
4.25
3.01E−02
3′ss
CLL



56874548-
56874548-
TCTGTGAATTTC
TCTGTGAACCAG









56875878
56875900
ACATCACTCATT
CTGAAAGAAACA











TAAC (554)
TTGG (555)











308
chr5:
chr5:
AGCATTGCTAGA
AGCATTGCTAGA
1
37
4.25
3.83E−05
3′ss
CLL



139815842-
139815842-
AGCAGCAGCTTT
AGCAGCAGGAAT









139818078
139818045
TGCAGATCCTGA
TGGCAAATTGTC











GGTA (19)
AACT (20)











309
chr22:
chr22:
TCATCAATGCCC
TCATCAATGCCC
0
18
4.25
3.60E−04
3′ss
CLL



24204389-
24204389-
CGACCTTGGTTC
CGACCTTGCACA









24209938
24210667
ATGAACACATTG
TTCAGGAATTCA











AGGT (556)
CCAA (545)











310
chr3:
chr3:
GCATTTCTGAGA
GCATTTCTGAGA
0
18
4.25
3.30E−03
3′ss
CLL



38038678-
38038678-
AGGCTCGGGTCC
AGGCTCGGGGGC









38038959
38038973
TCTCCCGCAGGG
TGGCTTTGACCT











GCTG (557)
ACAG (558)











311
chr6:
chr6:
GCCAGTCCAGAG
GCCAGTCCAGAG
1
36
4.21
6.38E−07
3′ss
CLL



109767078-
109767065-
CCCTCAAGTTCT
CCCTCAAGCTCT









109767338
109767338
TCTTCTCAGCTC
TGTGGCCATGGA











TTGT (559)
GAAG (560)











312
chr1:
chr1:
TGGCCGAGGCGC
TGGCCGAGGCGC
2
54
4.20
1.35E−04
3′ss
CLL



16803042-
16802999-
TGACCAAGACCT
TGACCAAGGCTG









16803424
16803424
TACTCAGGGGAT
AGGGCAGAGGAG











CCTC (561)
GCCT (562)











313
chr2:
chr2:
TCTACTTGGTGG
TCTACTTGGTGG
3
72
4.19
1.68E−04
3′ss
CLL



103348885-
103348868-
GCTTCTTGCATT
GCTTCTTGGATT









103353104
103353104
TATTTTGTTTTA
TGTTTGGTGTCA











GGAT (563)
GCAT (564)











314
chr14:
chr14:
GCTCCTGCTCAG
GCTCCTGCTCAG
0
17
4.17
3.99E−04
3′ss
CLL



78203438-
78203418-
TATATCCGTTTT
TATATCCGATAC









78205120
78205120
TATCTGCTTTCT
ACACCATCTCAG











TCAG (565)
CAAG (566)











315
chr3:
chr3:
GAAATAGGGCAC
GAAATAGGGCAC
0
17
4.17
7.71E−03
3′ss
CLL



122152652-
122152635-
AGATCCAGTTTT
AGATCCAGACTG









122156016
122156016
TCTTTAATTTTA
TGATAGATGCCA











GACT (567)
ACAT (568)











316
chr18:
chr18:
GCAACCTGTGTT
GCAACCTGTGTT
1
33
4.09
3.11E−03
3′ss
CLL



33724997-
33724997-
TTACAAAGGTTT
TTACAAAGATGG









33725896
33725910
TATTTTTTAGAT
TGTCCTACAGCA











GGTG (569)
GCCA (570)











317
chr7:
chr7:
GTATCAAAGTGT
GTATCAAAGTGT
1
33
4.09
4.37E−04
3′ss
CLL



94157562-
94157562-
GGACTGAGATTT
GGACTGAGGATT









94162500
94162516
GTCTTCCTTTAG
CCATTGCAAAGC











GATT (27)
CACA (28)











318
chr4:
chr4:
CCCCTGAAGTAC
CCCCTGAAGTAC
0
16
4.09
1.12E−04
3′ss
CLL



39868635-
39868617-
TAGCAAAGCATG
TAGCAAAGGTAC









39871013
39871013
TTAATATTTTAT
AGGCAATTAAAC











AGGT (571)
TTCT (572)











319
chr10:
chr10:
GTTCCTCACTTT
GTTCCTCACTTT
1
31
4.00
1.17E−04
3′ss
CLL



99502921-
99502921-
GAATGAGGTGTT
GAATGAGGGTGC









99504468
99504485
TTTGATTCTGCA
ATGGTACTCAGT











GGTG (573)
AGGT (574)











320
chr1:
chr1:
TCAGCCCTCTGA
TCAGCCCTCTGA
0
15
4.00
6.99E−03
3′ss
CLL



226036315-
226036255-
ACTACAAAGGTG
ACTACAAAACAG









226036597
226036597
TTTGTTCACAGA
AAGAGCCTGCAA











GATC (93)
GTGA (94)











321
chr20:
chr20:
TCTTGGAAGGCA
TCTTGGAAGGCA
0
15
4.00
4.25E−03
3′ss
CLL



31983014-
31982922-
GAGAAAAGATAT
GAGAAAAGTCTA









31984566
31984566
TTCTAGAGCATT
CCTCGAGACCTA











TGGG (575)
TGGC (576)











322
chr2:
chr2:
AACCCGGAGAGA
AACCCGGAGAGA
0
15
4.00
5.64E−03
3′ss
CLL



64456774-
64456774-
AAAGGGAGTTTG
AAAGGGAGCAAC









64456978
64478252
TTTTTAGGTCAG
TGATGTTGCCAT











AGTC (577)
GCAG (578)











323
chr11:
chr11:
AATCTTCCCGAA
AATCTTCCCCAA
1
30
3.95
7.37E−04
3′ss
CLL



92887382-
92887443-
GATGTATGTTCT
GATGTATGGTTA









92895871
92895871
ATGTTCCAGCAG
TATCAATCAGTG











AGAT (579)
AAAA (580)











324
chr18:
chr18:
CTCTCTTGTCAG
CTCTCTTGTCAG
1
30
3.95
2.23E−02
3′ss
CLL



43459192-
43459179-
ACAAGCAGTTGT
ACAAGCAGGTAA









43460039
43460039
CTCTTCCAGGTA
TGGAGACTATAC











ATGG (581)
AGTG (582)











325
chr5:
chr5:
GCAGAGCTGTGG
GCAGAGCTGTGG
1
30
3.95
1.23E−03
3′ss
CLL



138724290-
138724274-
CTTACCAGTCCC
CTTACCAGATGT









138725368
138725368
TCCTTGTTCCAG
GGCAAAATCTGG











ATGT (583)
CAAA (584)











326
chr17:
chr17:
TGCAGGAGACCG
TGCAGGAGACCG
1
29
3.91
7.83E−03
3′ss
CLL



58163509-
58163487-
GCTTTTGGGTCC
GCTTTTGGATAC









58165557
58165557
CCTTCTTATACC
TGCTAATCAGTC











CCTC (585)
CTAG (586)











327
chr1:
chr1:
AGTTACAACGAA
AGTTACAACGAA
1
29
3.91
2.95E−05
3′ss
CLL



185056772-
185056772-
CACCTCAGTGAC
CACCTCAGGAGG









185060696
185060710
TCTTTTACAGGA
CAATAACAGATG











GGCA (162)
GCTT (163)











328
chr10:
chr10:
TCTTGCCAGAGC
TCTTGCCAGAGC
0
14
3.91
5.04E−05
3′ss
CLL



99219232-
99219283-
TGCCCACGCTCT
TGCCCACGCTTC









99219415
99219415
CCACCCTCAGCT
TTTCCTTGCTGC











GCCT (587)
TGGA (588)











329
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
14
3.91
4.36E−02
3′ss
CLL



152022314-
152022314-
AATGGCAGCACC
AATGGCAGACAA









152024139
152024022
AACAGGTCCGCC
TGATTGAAGCTC











AAAT (344)
ACGT (345)











330
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
3
57
3.86
4.89E−06
3′ss
CLL



212515622-
212515622-
TACAACAGGTTT
TACAACAGCTCC









212519131
212519144
CTTTTAAAGCTC
TGGAGCTTTTTG











CTGG (65)
ATAG (66)











331
chr1:
chr1:
GCAGGCTGCCCG
GCAGGCTGCCCG
4
69
3.81
2.04E−07
3′ss
CLL



156552962-
156552962-
GGACTCTGGCTC
GGACTCTGGGGA









156553113
156553129
TCTTTCTCTCAG
CATGAAGGGACA











GGGA (589)
GTGG (590)











332
chr6:
chr6:
GCCAGTCCAGAG
GCCAGTCCAGAG
2
41
3.81
4.40E−03
3′ss
CLL



109767165-
109767065-
CCCTCAAGTCTT
CCCTCAAGCTCT









109767338
109767338
TACCAGACTTGC
TGTGGCCATGGA











AGGG (591)
GAAG (560)











333
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
5
81
3.77
1.48E−08
3′ss
CLL



34144042-
34144042-
ACGGAGAGGCTC
ACGGAGAGGTAC









34144725
34144743
CCCTCCCACCCC
TGAGGACAAATC











AGGT (49)
AGTT (50)











334
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
1
25
3.70
2.79E−05
3′ss
CLL



7131030-
7131102-
CCCCCGAACCTA
CCCCCGAAATGA









7131295
7131295
TCCAGGTTCCTC
GCCCATCCAGCC











CTCC (33)
AATT (34)











335
ch16:
ch16:
TTCCCACTGGTC
TTCCCACTGGTC
1
25
3.70
3.91E−03
3′ss
CLL



110085185-
110085185-
GCCTGCAGGTAT
GCCTGCAGACTG









110086201
110086215
TTCTCTTTAGAC
GCATCCTTCGAA











TGGC (592)
CCAA (593)











336
chr7:
chr7:
TGTAAATGGGGA
TGTAAATGGGGA
1
25
3.70
2.18E−05
3′ss
CLL



889240-
889240-
AGCGCTGTTTTC
AGCGCTGTGCGA









889468
889559
TACAGACTGCCA
CGACTGTAAGGG











TTGC (594)
CAAG (595)











337
chr12:
chr12:
TCAATGCAAATA
TCAATGCAAATA
0
12
3.70
1.92E−03
3′ss
CLL



112915534-
112915534-
TCATCATGGATT
TCATCATGCCTG









112915638
112915660
TTCTTCCTAAAT
AATTTGAAACCA











TTCT (596)
AGTG (597)











338
chr14:
chrU:
ACAAATCAACTG
ACAAATCAACTG
0
12
3.70
1.38E−03
3′ss
CLL



56100059-
56100059-
GAAAGCAATTAC
GAAAGCAAGCAG









56101230
56101243
TGTTTTCAGGCA
TCTGCAGAACTA











GTCT (598)
AATA (599)











339
chr17:
chr17:
CAAAGCGCCCAG
CAAAGCGCCCAG
0
12
3.70
2.10E−02
3′ss
CLL



2266428-
2266428-
CCCTGGGGGCTG
CCCTGGGGATCC









2266727
2266758
GAGGCTGAGCCC
GGAAACGGCACT











CGGC (600)
CAAG (601)











340
chr19:
chr19:
TGACACAGCCCT
TGACACAGCCCT
0
12
3.70
4.53E−05
3′ss
CLL



16264018-
16264018-
GCAGGCAGGACC
GCAGGCAGAAGG









16265158
16265208
TTTCCCCCTCCC
ATCCCGCAAACG











TAGT (602)
TGGA (511)











341
chr1:
chr1:
AGTTGCCATTCC
AGTTGCCATTCC
0
12
3.70
4.52E−03
3′ss
CLL



186324917-
186324900-
ATTACATGTCTT
ATTACATGCTTC









186325417
186325417
TACTTTCCTGAA
AAGCTTAGATGA











GCTT (603)
TGTT (604)











342
chr3:
chr3:
ACTGATTAAAAA
ACTGATTAAAAA
4
62
3.66
9.33E−05
3′ss
CLL



56649300-
56649300-
TCTTGGTGGTGA
TCTTGGTGTTGA









56649931
56649949
TTTCTCTTTGCC
TACAATACAAAT











AGTT (605)
GGAA (606)











343
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
4
58
3.56
3.53E−06
3′ss
CLL



10723474-
10723474-
TGAGACCGCTTG
TGAGACCGGTGC









10724788
10724802
TTTTCTGCAGGT
AGGCCTGGGGTA











GCAG (95)
GTCT (96)











344
chr3:
chr3:
AGGCTATTGTTG
AGGCTATTGTTG
1
22
3.52
2.36E−03
3′ss
CLL



184587316-
184587316-
CAGACCGGGCTG
CAGACCGGATGG









184588487
184588503
TTTTCCTTACAG
TAGAAATCCTAT











ATGG (607)
TCCA (608)











345
chr4:
chr4:
CCTTTCAAGAAA
CCTTTCAAGAAA
1
22
3.52
1.60E−02
3′ss
CLL



3124663-
3124663-
ACAAAAAGTCGC
ACAAAAAGGCAA









3125976
3127275
TTTTTCCAGTGG
AGTGCTCTTAGG











CGGT (609)
AGAA (610)











346
chr9:
chr9:
ACACGGAGCTCA
ACACGGAGCTCA
2
33
3.50
1.45E−05
3′ss
CLL



123933826-
123933826-
AGAAACAGTTTC
AGAAACAGATGG









123935634
123935520
TTCCAGAACTAC
CAAACCAAAAAG











CAGC (611)
ATTT (612)








347
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
6
76
3.46
9.28E−05
3′ss
CLL



5595521-
5595508-
AAGAGAGATTTT
AAGAGAGAAGCT









5598803
5598803
GGTAAACAGAGC
CCAAGAGTCAGG











TCCA (138)
ATCG (139)








348
chr5:
chr5:
GACTTCGAACAT
GACTTCGAACAT
4
54
3.46
7.66E−03
3′ss
CLL



78608321-
78608321-
TTAAACAGTGTG
TTAAACAGAGGT









78610192
78610079
TTACAGGTAGAA
ATCCTGGGCAAG











GAGA (613)
TCAT (614)








349
chr2:
chr2:
ACCACGAAGGGT
ACCACGAAGGGT
2
32
3.46
1.25E−02
3′ss
CLL



231050873-
231050859-
CACACAAGTCTA
CACACAAGGGGC









231065600
231065600
TTTGGTCCAGGG
AGCCTCACCTGG











GCAG (615)
GCAT (616)











350
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
1
21
3.46
1.57E−05
3′ss
CLL



52880319-
52880319-
AGGAGAAGTCTG
AGGAGAAGCCCC









52880412
52880433
ACCAGTCTTTTC
TCCCCTCGCCGA











TACA(55)
GAAA{56)











351
chr2:
chr2:
TTAACAAACACG
TGCTGGCACACC
0
10
3.46
8.22E−03
5′ss
CLL



69015785-
69015088-
TGAATCTACAGT
CTGTGGAGCAGT









69034404
69034404
GTTTGGCCAGCG
GTTTGGCCAGCG











CTTG{617)
CTTG{618)











352
chr5:
chr5:
CGCCCCAGGGCA
CGCCCCAGGGCA
0
10
3.46
1.97E−03
3′ss
CLL



156915521-
156915497-
AGCGAAAGGTGT
AGCGAAAGGTGA









156916109
156916109
TCCTTGACTTGT
TCAACACTCCGG











GCGT(619)
AAAT{620)











353
chr9:
chr9:
TGGTACAACTTC
TGGTACAACTTC
0
10
3.46
6.70E−03
3′ss
CLL



115934002-
115933986-
AGGAAAAGTCTG
AGGAAAAGTGTT









115935732
115935732
TTTGTTTTGCAG
TAGCCCTCCAGG











TGTT{621)
CCCA{622)











354
chr14:
chr14:
TGGATTTGCTCG
TGGATTTGCTCG
1
20
3.39
1.52E−04
3′ss
CLL



50808004-
50807950-
gcttttgatttt
GCTTTTGACTGG









50808849
50808849
GATTCCAGCCTT
ACCGAGTGACTA











CCGC{623)
CTAT{624)











355
chr18:
chr18:
GATGAGGACCCC
GATGAGGACCCC
5
61
3.37
3.06E−06
3′ss
CLL



9133520-
9133508-
CACATAGGTTTC
CACATAGGGATG









9136361
9136361
CAAACCAGGATG
GCCATAGCAGCC











GCCA{625)
ACAA{626)











356
chr10:
chr10:
TACCTCTGGTTC
TACCTCTGGTTC
3
39
3.32
2.21E−05
3′ss
CLL



99214556-
99214556-
CTGTGCAGTCTT
CTGTGCAGTTCT









99215395
99215416
CGCCCCTCTTTT
GTGGCACTTGCC











CTTA{13)
CTGG{14)











357
chr2:
chr2:
TGTTTTAAATTC
TGTTTTAAATTC
2
29
3.32
8.44E−06
3′ss
CLL



225670231-
225670246-
CATAGCAGCTAT
CATAGCAGCATT









225670842
225670842
TTCTACAGTAAA
TTCATCAATAGC











CCAT{627)
TATT{628)











358
chrX:
chrX:
GCTGGGATGTTA
GCTGGGATGTTA
1
19
3.32
2.06E−02
3′ss
CLL



153323986-
153298008-
GGGCTCAGCCTG
GGGCTCAGGGAA









153357641
153357641
TCGTTCCAGGAC
GAAAAGTCAGAA











CCAG{629)
GACC{630)











359
chr16:
chr16:
CTGGTTATTGCA
CTGGTTATTGCA
0
9
3.32
6.10E−05
3′ss
CLL



72139523-
72139523-
AATTAAAGCTCT
AATTAAAGGTCT









72139882
72139903
TTGCCGTCCCCT
TCAACCCCAGGA











CCTA{631)
TTGG{632)











360
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
4
48
3.29
1.01E−06
exon
CLL



869519-
865696-
CTCTCTGGTTTC
CTCTCTGGGGAA




incl.




870587
870587
TTTCAGGGCCTG
GGTGAAGAAGGA











CCAT{128)
GCTG{129)











361
chrX:
chrX:
GGTCATGCTAAT
GGTCATGCTAAT
8
82
3.21
5.22E−07
3′ss
CLL



70516897-
70516897-
GAGACAGGTCTG
GAGACAGGATTT









70517210
70517226
TTGTTTTTTTAG
GATGAGGCGCCA











ATTT{633)
AGAA{634)











362
chr16:
chr16:
GTCAGCATTTGC
GTCAGCATTTGC
2
26
3.17
7.43E−04
3′ss
CLL



47347747-
47347734-
AGACTTTGTTTC
AGACTTTGATGG









47399698
47399698
TTTTGGCAGATG
AGATGGACACAT











GAGA{635)
GGAT{636)











363
chr5:
chr5:
GCAGAGCTGTGG
GCAGAGCTGTGG
2
26
3.17
1.17E−03
3′ss
CLL



138725125-
138724274-
CTTACCAGACTT
CTTACCAGATGT









138725368
138725368
CTCCCTTTCCAG
GGCAAAATCTGG











GCCC{637)
CAAA{584)











364
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
8
3.17
6.70E−03
3′ss
CLL



62648919-
62648919-
CCTGGCGGCCCC
CCTGGCGGGTCT









62649352
62649364
CATTTCAGGTCT
GAAGGGGCGTCT











GAAG (165)
CGAT (166)











365
chr11:
chr11:
TGCAGCTGGCCC
TGCAGCTGGCCC
0
8
3.17
2.22E−02
3′ss
CLL



64002365-
64002365-
CCGCCCAGGTCT
CCGCCCAGGCCC









64002911
64002929
TTTCTCTCCCAC
CTGTCTCCCAGC











AGGC (638)
CTGA (639)











366
chr14:
chrU:
CACAGCAAGCAC
CACAGCAAGCAC
0
8
3.17
3.01E−05
3′ss
CLL



31169464-
31169464-
CTTCTGAGTTCT
CTTCTGAGGCTG









31171484
31171501
TTTCTTATTTCA
ATTTGGAGCAAT











GGCT (640)
ATAA (641)











367
chr1:
chr1:
TCACACCTGTAG
TCACACCTGTAG
0
8
3.17
9.33E−05
3′ss
CLL



186300728-
186300711-
GAACTGAGTGTA
GAACTGAGGAAG









186301326
186301326
TTATGATACAGG
AAGTTATGGCAG











AAGA (642)
AAGA (643)











368
chr5:
chr5:
AAAATTGACTAT
AAAATTGACTAT
0
8
3.17
7.30E−03
3′ss
CLL



169101449-
169101449-
GGCAACAATTTT
GGCAACAAAATC









169108733
169108747
TGCTTTACAGAA
CTTGAGCTTGAT











TCCT (644)
TTGA (645)











369
chr9:
chr9:
ACACGGAGCTCA
ACACGGAGCTCA
0
8
3.17
5.42E−04
3′ss
CLL



123933826-
123933826-
AGAAACAGAACT
AGAAACAGATGG









123935644
123935520
ACCAGCAGATCT
CAAACCAAAAAG











AGAA (646)
ATTT (612)











370
chr10:
chr10:
GGGAGGAAAAGT
GGGAGGAAAAGT
5
52
3.14
1.27E−03
3′ss
CLL



112058568-
112058548-
AATTAATGTTTT
AATTAATGGAAG









112060304
112060304
TGTTTTTCTTTT
TTATAGAACTAA











TTAG (647)
CCAA (648)











371
chr3:
chr3:
ATTTGGATCCTG
ATTTGGATCCTG
4
43
3.14
1.46E−04
3′ss
CLL



196792335-
196792319-
TGTTCCTCTTTT
TGTTCCTCATAC









196792578
196792578
TTTCTGTTAAAG
AACTAGACCAAA











ATAC (87)
ACGA (88)











372
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
3
34
3.13
1.20E−04
3′ss
CLL



105601825-
105601807-
TAGCAATGATGT
TAGCAATGAGCA









105601935
105601935
CTGTTTATTTTT
TGACCTCTCAAT











AGAG (41)
GGCA (42)











373
chr19:
chr19:
CTATGGGCTCAC
CTATGGGCTCAC
7
67
3.09
2.90E−04
3′ss
CLL



41084118-
41084118-
TCCTCTGGTCCT
TCCTCTGGTTCG









41084353
41084367
CCTGTTGCAGTT
TCGCCTGCAGCT











CGTC (169)
TCGA (170)











374
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
1
16
3.09
4.69E−03
3′ss
CLL



125442465-
125442465-
TTGCCAGACCTT
TTGCCAGAGGAA









125445146
125445158
TTCTATAGGGAA
TCAAAGACTCCA











TCAA (150)
TCTG (151)











375
chr12:
chr12:
AGAAGGAGCTGC
AGAAGGAGCTGC
1
16
3.09
2.88E−03
3′ss
CLL



110437589-
110437589-
AGGGCCAGTGTT
AGGGCCAGAATG









110449795
110449809
TCCTTCACAGAA
TGGAGGCTGTGG











TGTG (649)
ACCC (650)











376
chr8:
chr8:
GCTCTGGAGAAT
GCTCTGGAGAAT
4
41
3.07
6.90E−07
3′ss
CLL



126051218-
126051201-
CTCAATAAGGTT
CTCAATAAGGCT









126052036
126052036
TTTCTTCCTTTA
CTCCTAGCAGAC











GGGC (651)
ATTG (652)











377
chr3:
chr3:
CATGCAATGAAC
CATGCAATGAAC
2
24
3.06
7.00E−06
3′ss
CLL



42674315-
42674315-
CCAAAAGGTTGA
CCAAAAGGTCAC









42675109
42675071
TTCCAGTGCTAA
TCTGAGAGGAGT











AAGG (653)
GATA (654)











378
chr5:
chr5:
TGCTTCCGGAAC
TGCTTCCGGAAC
6
57
3.05
3.26E−05
3′ss
CLL



139941307-
139941286-
AGTGACAGCCCC
AGTGACAGGGAC









139941428
139941428
ATCTCTGCCCCT
TTCGCTTTTGTG











GCTA (655)
GCAA (656)











379
chr12:
chr12:
TGGGTTTCAGCA
TGGGTTTCAGCA
0
7
3.00
4.31E−03
3′ss
CLL



64199184-
64199184-
AGAGAACATTGT
AGAGAACACTGG









64202434
64202454
TTTTCTGATTTT
CAGCCTCAGGAA











CTAG (657)
ACAA (658)











380
chr18:
chr18:
AGGACATGGATT
AGGACATGGATT
0
7
3.00
4.13E−03
3′ss
CLL



47311742-
47311721-
TGGTAGAGTGCT
TGGTAGAGGTGA









47313660
47313660
CTAATTTTTGTT
ATGAAGCTTTTG











TTAA (659)
CTCC (660)











381
chr19:
chr19:
ATCACAACCGGA
ATCACAACCGGA
0
7
3.00
2.46E−02
3′ss
CLL



15491444-
15491423-
ACCGCAGGCTCC
ACCGCAGGCTCA









15507960
15507960
TTCTGCCCTGCC
TGATGGAGCAGT











CGCA (661)
CCAA (662)











382
chr1:
chr1:
CAGGAAGCAGCT
CAGGAAGCAGCT
0
7
3.00
7.09E−04
3′ss
CLL



46068037-
46068037-
agtcttttatgt
AGTCTTTTAGGT









46070588
46070607
TTATTCTCTTTG
AAGAAGTATGGA











TAGA (663)
GAGA (664)











383
chr21:
chr21:
GAACCAATGGAA
GAACCAATGGAA
0
7
3.00
1.40E−02
3′ss
CLL



45452053-
45452053-
TGGAGAAGGCAC
TGGAGAAGGTCC









45452682
45457672
AGGCGTTTTGCA
TATGGCCGGGCT











AAGG (665)
CCGA (666)











384
chr2:
chr2:
TGCTTGTAAAAT
TGCTTGTAAAAT
0
7
3.00
1.13E−02
3′ss
CLL



160673561-
160673543-
TGAAATGGTGCT
TGAAATGGTTGA









160676236
160676236
TTTAATTATTAT
CTACAAAGAAGA











AGTT (667)
ATAT (668)











385
chr5:
chr5:
ACTCGCGCCTCT
ACTCGCGCCTCT
0
7
3.00
4.59E−02
3′ss
CLL



150411955-
150411944-
TCCATCTGTTTT
TCCATCTGCCGG









150413168
150413168
GTCGCAGCCGGA
AATACACCTGGC











ATAC (109)
GTCT (110)











386
ch17:
chr7:
CCACCTCACCAT
CCACCTCACCAT
0
7
3.00
2.08E−02
3′ss
CLL



99954506-
99954506-
CACCCAGGCCCC
CACCCAGGCCCT









99955853
99955842
TCCACAGGGCCC
CAGGCAGCCCCT











CTCT (669)
CCAC (515)











387
chr4:
chr4:
CGTCTCCATGAC
CGTCTCCATGAC
6
54
2.97
7.33E−05
3′ss
CLL



995351-
995351-
CATGCAAGGTGT
CATGCAAGGCTT









995438
995466
AGACGCAGTGCT
CCTGAACTACTA











CCCC (670)
CGAT (671)











388
chr15:
chr15:
AGGAGGCAATTA
AGGAGGCAATTA
8
68
2.94
1.81E−04
3′ss
CLL



75131104-
75131086-
AGGCAAAGGCCC
AGGCAAAGGTGG









75131350
75131350
TTTCCCTGCTAC
GGCAGTACGTGT











AGGT (672)
CCCG (673)











389
chrX:
chrX:
TACAAGAGCTGG
TACAAGAGCTGG
2
22
2.94
1.26E−04
3′ss
CLL



153699660-
153699660-
GTGGAGAGGGTC
GTGGAGAGGTAT









153699819
153699830
CCAACAGGTATT
TATCGAGACATT











ATCG (158)
GCAA (159)











390
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
5
43
2.87
3.76E−08
3′ss
CLL



125023777-
125023787-
GCCACGAGACAT
GCCACGAGTATT









125026993
125026993
TGATGGAAGCAG
TCATAGACATTG











AAAC (142)
ATGG (143)











391
chr14:
chr14:
TTACCTCCGAAG
TTACCTCCGAAG
10
79
2.86
3.40E−05
3′ss
CLL



23242937-
23242925-
GATCGTGGTTCT
GATCGTGGGGTC











CTTTGTAGGGTC
TGCCACAAGGTA









23243141
23243141
TGCC (674)
CCTC (675)











392
chr11:
chr11:
AATAAGCCCTCA
AATAAGCCCTCA
0
6
2.81
1.66E−02
3′ss
CLL



67376193-
67376193-
GATGGCAGCCTG
GATGGCAGGCCC









67376896
67376922
TCTGACCTGTGG
AAGTATCTGGTG











GCCC(676)
GTGA{677)











393
chr16:
chr16:
ACTCCCAGCTCA
ACTCCCAGCTCA
0
6
2.81
1.49E−02
3′ss
CLL



56403209-
56403239-
ATGCAATGGTTC
ATGCAATGGCTC









56419830
56419830
CATACCATCTGG
ATCAGATTCAAG











TACT{332)
AGAT{333)











394
chr17:
chr17:
GCCTGGACCTGT
GCCTGGACCTGT
0
6
2.81
4.26E−02
3′ss
CLL



43316432-
43316432-
ACTTGGAGGTGC
ACTTGGAGAGGC









43317875
43317842
AGATCCAGGCGT
TTCGGCTCACCG











ACCT(678)
AGAG{679)











395
chr21:
chr21:
CTGTAACTACTA
CTGTAACTACTA
0
6
2.81
3.47E−04
3′ss
CLL



47655360-
47655340-
GCCCACAGTTTC
GCCCACAGAGTG









47656742
47656742
TTTTTTATTCAA
ACATGATGAGGG











ATAG{680)
AGCA{681)











396
chr3:
chr3:
CTCTCAATGCAG
CTCTCAATGCAG
0
6
2.81
1.49E−03
3′ss
CLL



71019345-
71015207-
CTTTACAGTTTT
CTTTACAGGCTT









71019886
71019886
CCTGCAGATTGT
CAATGGCTGAGA











TCAA{682)
ATAG{683)











397
chr9:
chr9:
GGAGCAGTTCCA
GGAGCAGTTCCA
0
6
2.81
4.44E−03
3′ss
CLL



95007367-
95007353-
GAAGACTGCTGC
GAAGACTGGGAC









95009658
95009658
TTCTCCATAGGG
CATTGTTGTGGA











ACCA{684)
AGGC{685)











398
chrX:
chrX:
CCTGCTGGACCA
CCTGCTGGACCA
0
6
2.81
1.25E−02
3′ss
CLL



48340103-
48340103-
TTCTTACGTTGT
TTCTTACGATTT









48340769
48340796
CTCCCCCTGTTC
CAACCAGCTGGA











CTAA{686)
TGGT{687)











399
chr20:
chr20:
GGATTTTGATAA
GGATTTTGATAA
7
53
2.75
1.01E−03
3′ss
CLL



36631195-
36631178-
TGAAGAAGTTGT
TGAAGAAGAGGA









36634598
36634598
GCTCTTTTTCCA
ACAGTCAGTCCC











GAGG{688)
TCCC{689)











400
chr4:
chr4:
CGTCTCCATGAC
CGTCTCCATGAC
3
26
2.75
5.89E−04
3′ss
CLL



995351-
995351-
CATGCAAGGGCA
CATGCAAGGCTT









995433
995466
GGTGTAGACGCA
CCTGTAACTACTA











GTGC{690)
CGAT{671)











401
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
2
19
2.74
3.63E−05
3′ss
CLL



25213229-
25213229-
AAAACCAGCCTT
AAAACCAGGCTC









25219533
25219457
CCCCTAGGTCTT
CATCTACTCTTT











CAGA{230)
GAAG{231)











402
chr18:
chr18:
AGTGCCAGCTGC
AGTGCCAGCTGC
2
19
2.74
1.04E−03
exon
CLL



47811617-
47811721-
GGGCCCGGCTCT
GGGCCCGGGAAT




skip




47812118
47812118
CACCAGTGACGC
CGTACAAGTACT











CCTC{691)
TCCC{692)











403
chr18:
chr18:
AACTTACTTTGT
AACTTACTTTGT
2
19
2.74
1.46E−04
3′ss
CLL



66356291-
66355002-
TTATGATGCTTT
TTATGATGAGTA









66358531
66358531
TATTTTAGATTC
TGAAGATGGTGA











AGAG{693)
TCTG{694)











404
chr21:
chr21:
ATCATAGCCCAC
ATCATAGCCCAC
3
25
2.7
2.17E−02
3′ss
CLL



37416267-
37416254-
ATGTCCAGTTTT
ATGTCCAGGTAA









37417879
37417879
TCTTTCTAGGTA
AAGCAGCGTTTA











AAAG{695)
ATGA{696)











405
chrX:
chrX:
TGACTCCGCTGC
TGACTCCGCTGC
1
12
2.7
2.07E−02
3′ss
CLL



118923962-
118923974-
TCGCCATGACTT
TCGCCATGTCTT









118925536
118925536
TCAGGATTAAGC
CTCACAAGACTT











GATT{697)
TCAG{698)











406
chr1:
chr1:
CCAAGCACCTGA
CCAAGCACCTGA
7
50
2.67
1.87E−03
3′ss
CLL



100606070-
100606070-
AACAGCAGTTTG
AACAGCAGATGC









100606400
100606522
CAGGCTTCTATT
TGAAAAAGTTCA











TTAG (699)
CTTC (700)











407
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
13
88
2.67
1.74E−07
3′ss
CLL



113346629-
113346629-
TGCCCTGGATTT
TGCCCTGGGTCA









113348840
113348855
TGCCCGAACAGG
GTTGACTGGCGG











TCAG (71)
CTAT (72)











408
ch17:
chr7:
CGAGCTGTTGGC
CGAGCTGTTGGC
7
49
2.64
2.27E−05
3′ss
CLL



149547427-
149547427-
ATCCTTGGTTTC
ATCCTTGGGACC









149549949
149556510
TTGTCCACAGGA
TGCCGCTGCCAA











GAAG (701)
GCCA (702)











409
chr11:
chr11:
GCTTTCTACGGA
GCTTTCTACGGA
3
24
2.64
1.08E−04
3′ss
CLL



126142974-
126142974-
ACATCAATGAGC
ACATCAATGAGT









126143210
126143230
TTCTGTCTGCAC
ACCTGGCCGTAG











ACAG (703)
TCGA (704)











410
chr8:
chr8:
TTATTTTACACA
TTATTTTACACA
3
24
2.64
2.89E−05
3′ss
CLL



38095145-
38095145-
ATCCAAAGCCAG
ATCCAAAGCTTA









38095624
38095606
TTGCAGGGTCTG
TGGTGCATTACC











ATGA (57)
AGCC (58)











411
chr12:
chr12:
CAGGAATACCTG
CAGGAATACCTG
1
11
2.58
2.06E−06
3′ss
CLL



62783294-
62783294-
CAGATAAGATTT
CAGATAAGATGA









62783413
62783384
CACAGAATATTC
TAGTTACTGATA











GCTA (705)
TATA (706)











412
chr17:
chr17:
CTACACCAAGAA
CTACACCAAGAA
1
11
2.58
2.56E−03
3′ss
CLL



18007203-
18007203-
GAGAGGACCTCT
GAGAGGACAGAG









18007857
18007936
TCCCTCGCGCAG
GCCAGACTTCAC











AATC (707)
AGAC (708)











413
chr17:
chr17:
CGGAGGCTGTCT
CGGAGGCTGTCT
1
11
2.58
4.39E−03
3′ss
CLL



73486839-
73486839-
CCTCTCAGACTT
CCTCTCAGGAAA









73487110
73487129
CCTCTCTCCCAC
TGCTGCGCTGCA











CAGG (709)
TTTG (710)











414
chr11:
chr11:
TCCTGCTGGAGC
TCCTGCTGGAGC
0
5
2.58
5.77E−03
3′ss
CLL



68331900-
68331900-
CACCCAAGCTTT
CACCCAAGAAAA









68334466
68334481
TTCTTCTTCAGA
GTGTGATGAAGA











AAAG (711)
CCAC (712)











415
chr13:
chr13:
AGCTGAAATTTC
AGCTGAAATTTC
0
5
2.58
3.85E−02
3′ss
CLL



113915073-
113915073-
CAGTAAAGGGGG
CAGTAAAGCCTG









113917776
113917800
gttttattcttc
GAGATTTGAAAA











TTTT (152)
AGAG (153)











416
chr13:
chr13:
ACCAAGCATACT
ACCAAGCATACT
0
5
2.58
1.04E−02
3′ss
CLL



20656270-
20656270-
TCCAGATGTTCT
TCCAGATGGGTC









20656905
20656920
CTCTATTTAAGG
AATATTCTCTCG











GTCA (713)
AGTT (714)











417
chr19:
chr19:
CGGGCCGCCCCC
CGGGCCGCCCCC
0
5
2.58
1.76E−03
3′ss
CLL



36231397-
36230989-
CTGCCCGGTGTT
CTGCCCGGAGGC









36231924
36231924
CTTCTGGGCAGT
CGGTCCCTGCCA











GCAA (715)
AGGG (716)











418
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
5
2.58
3.36E−03
3′ss
CLL



34144042-
34144042-
ACGGAGAGTTCT
ACGGAGAGGTAC









34144761
34144743
CTGTGACCAGAC
TGAGGACAAATC











ATGA (250)
AGTT (50)











419
chr21:
chr21:
AAGATGTCCCTG
AAGATGTCCCTG
0
5
2.58
3.03E−02
3′ss
CLL



38570326-
38570326-
TGAGGATTGTGT
TGAGGATTGCAC









38572514
38572532
GTTTGTTTCCAC
TGGGTGCAAGTT











AGGC (224)
CCTG (225)











420
chr6:
chr6:
GGAGGACTGGGG
GGAGGACTGGGG
0
5
2.58
2.97E−03
3′ss
CLL



32095539-
32095527-
TCTGCAGACATT
TCTGCAGAACAG









32095893
32095893
TCTTGCAGACAG
CACCTTGTATTC











CACC (717)
TGGC (718)











CTGCCCCCTGCG
CTGCCCCCTGCG
0
5
2.58
7.48E−03
3′ss
CLL





421
chr7:
chr7:
CCACACGGCCTC
CCACACGGTGAT









44795898-
44795898-
TTTCCCTGCAGT
GGTTCATTCGCA









44796008
44796023
GATG (719)
TATG (720)











TGTAAATGGGGA
TGTAAATGGGGA
0
5
2.58
2.68E−02
3′ss
CLL





422
chr7:
chr7:
AGCGCTGTACTG
AGCGCTGTGCGA









889240-
889240-
CCATTGCTATGC
CGACTGTAAGGG









889477
889559
ACGG (721)
CAAG (595)











GGCCAGCCCCCT
GGCCAGCCCCCT
10
62
2.52
1.37E−08
3′ss
CLL





423
chr12:
chr12:
TCTCCACGGCCT
TCTCCACGGTAA









120934019-
120934019-
TGCCCACTAGGT
CCATGTGCGACC









120934204
120934218
AACC (206)
GAAA (207)











CTGATGAAAACT
CTGATGAAAACT
11
66
2.48
1.51E−04
3′ss
CLL





424
chr9:
chr9:
ACTACAAGCAGA
ACTACAAGGCCC









93641235-
93641235-
CACCTTACAGGC
AGACCCATGGAA









93648124
93650030
CAGG (722)
AGTG (723)











TTCAGCTGCCCC
TTCAGCTGCCCC
8
49
2.47
1.42E−05
3′ss
CLL





425
chr17:
chr17:
TGAAGAAGAAAC
TGAAGAAGGAAT









57079102-
57079075-
ATGTTCTCCTTC
GAGTAGCGACAG









57089688
57089688
CTTC (724)
TGAC (725)











GAAACCAACTAA
GAAACCAACTAA
3
21
2.46
9.18E−03
3′ss
CLL





426
chr15:
chr15:
AGGCAAAGCCCA
AGGCAAAGGTAA









59209219-
59209198-
TTTTCCTTCTTT
AAAACATGAAGC









59224554
59224554
CGCA (101)
AGAT (102)











TCCCGAAGCCAC
TCCCGAAGCCAC
3
21
2.46
4.67E−04
3′ss
CLL





427
chr7:
chr7:
CTCATGAGCCTC
CTCATGAGGTCG









99752804-
99752787-
TGCCTTCCCCCA
GGCAGTGTGATG









99752884
99752884
GGTC (726)
GAGC (727)











CCCCGGTGCGTA
CCCCGGTGCGTA
1
10
2.46
2.22E−02
3′ss
CLL





428
chr8:
chr8:
AGGAGGAGCCTG
AGGAGGAGGAGG









145624052-
145624028-
CCCCCCTTTGGC
ACAATCCCAAGG









145624168
145624168
CCTG (728)
GGGA (729)











AGCTGGAGAAAA
AGCTGGAGAAAA
1
10
2.46
3.34E−04
3′ss
CLL





429
chr9:
chr9:
ACCTTCTTTTTC
ACCTTCTTATGG









123932094-
123932094-
TTCCAGAACTAC
CAAACCAAAAAG









123935634
123935520
CAGC (730)
ATTT (731)











TTCGTTGGCAGC
TTCGTTGGCAGC
6
37
2.44
2.59E−04
3′ss
CLL





430
chr15:
chr15:
TTCTGCTGAGAC
TTCTGCTGCGTC









77327904-
77327904-
CCTGACCCCCAC
CACAGAGACCCT









77328151
77328142
CCCC (732)
GACC (733)











GTGCTTGGAGCC
GTGCTTGGAGCC
5
31
2.42
4.69E−03
3′ss
CLL





431
chr19:
chr19:
CTGTGCAGACTT
CTGTGCAGCCTG









55776746-
55776757-
TCCGCAGGGTGT
GTGACAGACTTT









55777253
55777253
GCGC (179)
CCGC (180)











GTGCCAACGAGG
GTGCCAACGAGG
10
57
2.4
1.64E−03
3′ss
CLL





432
chr4:
chr4:
ACCAGGAGTTCT
ACCAGGAGATGG









184577127-
184577114-
TTATTTCAGATG
AACTAGAAGCAT









184580081
184580081
GAAC (734)
TACG (735)











CCTCACGATGCA
CCTCACGATGCA
7
40
2.36
8.53E−04
3′ss
CLL





433
chr16:
chr16:
AGGCCACGAGTT
AGGCCACGGGAG









67692735-
67692719-
CATGTCCCACAG
AAGCTGTGTACA









67692830
67692830
GGAG (736)
CTGT (737)











434
chr6:
chr6:
AGGGGGCTCTTT
AGGGGGCTCTTT
14
75
2.34
3.51E−06
3′ss
CLL



91269953-
91269933-
ATATAATGTTTG
ATATAATGTGCT









91271340
91271340
TGCCTTTCTTTC
GCATGGTGCTGA











GCAG (265)
ACCA (266)











435
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
2
14
2.32
4.92E−03
exon
CLL



25212299-
25207356-
ATTTGAAAGTGT
AACCAAGAGTGT




incl.




25213078
25213078
CAGTTGTACCCG
CAGTTGTACCCG











AGGC (164)
AGGC (145)











436
chr9:
chr9:
AAAAATAAAGCC
CTGATGAAAACT
1
9
2.32
3.99E−03
5′ss
CLL



93648256-
93641235-
TTTCCCAGGCCC
ACTACAAGGCCC









93650030
93650030
AGACCCATGGAA
AGACCCATGGAA











AGTG (738)
AGTG (723)











437
chr14:
chr14:
CGAGGATGAAGA
CGAGGATGAAGA
0
4
2.32
4.50E−03
3′ss
CLL



34998676-
34998681-
CAGAGCAGGTGA
CAGAGCAGTACA









35002649
35002649
CCAAGAAAAAAA
GGTGACCAAGAA











AGAA (739)
AAAA (740)











438
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
4
2.32
1.21E−02
3′ss
CLL



26437445-
26437430-
GGTGGAAACATT
GGTGGAAAAATT









26437921
26437921
TTATTTTACAGA
GACAGCGTATGC











ATTG (295)
CATG (296)











439
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
16
82
2.29
2.84E−08
3′ss
CLL



129771378-
129771384-
GGAATCAGTATC
GGAATCAGCCTT









129790554
129790554
ACAGGCAGAAGC
AGTATCACAGGC











TCTG (303)
AGAA (304)











440
chr1:
chr1:
TTCCCCATCAAC
TTCCCCATCAAC
5
28
2.27
4.85E−06
3′ss
CLL



19480448-
19480433-
ATCAAAAGTTTT
ATCAAAAGTTCC









19481411
19481411
GTTGTCTGCAGT
AATGGTGGCAGT











TCCA (202)
AAGA (203)











441
chr3:
chr3:
AAAATGGGCTCA
AAAATGGGCTCA
10
52
2.27
1.39E−04
3′ss
CLL



141896447-
141896418-
GCAGTTAGGGTT
GCAGTTAGACCT









141900302
141900302
TTTTGTTGTTTG
TTTCACAGATGC











TTTG (741)
TGCT (742)











442
chr1:
chr1:
AAGCACTGGCCC
AAGCACTGGCCC
4
22
2.20
2.08E−02
3′ss
CLL



156553242-
156553242-
AGTGTCAGGAGC
AGTGTCAGAAGG









156553591
156553588
CAGATTCTGTGC
AGCCAGATTCTG











GAGA (743)
TGCG (744)











443
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
11
53
2.17
2.14E−08
3′ss
CLL



9728842-
9728855-
GTCCCGTGGGAA
GTCCCGTGGGTT









9730107
9730107
CCAATCTGCCCT
TTTTTCCAGGGA











TTTG (160)
ACCA (161)











444
chr15:
chr15:
CCACTCTCACAA
CCACTCTCACAA
1
8
2.17
1.41E−02
3′ss
CLL



91448953-
91448953-
TGACCCAGGAGG
TGACCCAGGCTG









91449151
91449074
ACCCCCGGCGGC
GATCAAGACCTT











GCTT (745)
TGAC (746)











445
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
8
2.17
4.59E−02
3′ss
CLL



23398690-
23398690-
CCCCCAAGTCCT
CCCCCAAGTGAT









23399766
23399784
TTGTTCTTTTGC
GTATATCTCTCA











AGTG (210)
TCAA (211)











446
chr2:
chr2:
CCTTTACTTGGG
AACCCGGAGAGA
1
8
2.17
4.13E−02
5′ss
CLL



64457092-
64456774-
GCTCTCAGCAAC
AAAGGGAGCAAC









64478252
64478252
TGATGTTGCCAT
TGATGTTGCCAT











GCAG (747)
GCAG (578)











447
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
16
75
2.16
9.79E−09
3′ss
CLL



23237380-
23237380-
TGCTGCATTTTG
TGCTGCATGTAC









23238985
23238999
TATTTTCCAGGT
AGTCTTTGCCCG











ACAG (122)
CTGC (123)











448
chr15:
chr15:
ACTCAGATGCCG
ACTCAGATGCCG
14
65
2.14
1.32E−05
3′ss
CLL



74326871-
74326871-
AAAACTCGCCCT
AAAACTCGTGCA









74327483
74327512
CAGTCTGAGGTT
TGGAGCCCATGG











CTGT (748)
AGAC (749)











449
chr10:
chr10:
GCCTACTCTTAA
TCATCTTGAAAA
7
34
2.13
4.92E−03
exon
CLL



89516679-
89516679-
CCATTAGGGTGG
ATGAAAATGTGG




incl.




89519457
89527429
ATAGGCATGTAG
ATAGGCATGTAG











ACCT (750)
ACCT (507)











450
chr20:
chr20:
TGGAGTGCGGAT
TGGAGTGCGGAT
2
12
2.12
4.37E−03
3′ss
CLL



33703761-
33703736-
TTGCAACACTTG
TTGCAACAATCA









33706400
33706400
CTTCCTTCTCCC
AAGATCTGCGAG











ACAT (751)
ACCA (752)











451
chr12:
chr12:
CAACTGGAGTTC
CAACTGGAGTTC
12
53
2.05
3.67E−06
3′ss
CLL



105514375-
105514375-
ATTTTCAGGTTT
ATTTTCAGACTA









105514866
105514878
TTTGACAGACTA
TGTATGAGCACT











TGTA (753)
TGGG (754)











452
chr1:
chr1:
CAATGTGTTGAC
CAATGTGTTGAC
14
61
2.05
1.87E−03
3′ss
CLL



155237988-
155237937-
CATCGCAGTCCC
CATCGCAGCCTC









155238083
155238083
CCTACAGCCCTG
TCCTGCCAACTT











TTCA (755)
ACAG (756)











453
chr15:
chr15:
CAGCTGCTCTCA
CAGCTGCTCTCA
16
67
2.00
7.47E−04
3′ss
CLL



89870310-
89870294-
GGAGAGAGTGGA
GGAGAGAGGTAC









89870397
89870397
CTGGCTCTGTAG
AAAGAAGACCCC











GTAC (757)
TGGC (758)











454
chr3:
chr3:
TCTCTAGTGGGC
TCTCTAGTGGGC
8
35
2.00
7.53E−03
3′ss
CLL



141272782-
141272782-
CCTTCTAGTTCT
CCTTCTAGGAAT









141274647
141274681
ACAAGGTAAAAC
GACCAAAAGAAG











TCTA (759)
ACAA (760)











455
chr1:
chr1:
AGCTCCGAGAGG
AGCTCCGAGAGG
2
11
2.00
6.28E−03
3′ss
CLL



202122978-
202122963-
GCAAGGAGCTCC
GCAAGGAGAAAT









202123313
202123313
CTCCCTCCTAGA
GTGTCCACTACT











AATG (761)
GGCC (762)











456
chrX:
chrX:
GACGTGGCAGCT
GACGTGGCAGCT
19
73
1.89
1.20E−04
3′ss
CLL



47315813-
47315797-
CATGTGAGCATT
CATGTGAGGCTT









47326808
47326808
GTGTCGTTACAG
CAGTGTCATTTG











GCTT (763)
AGGA (764)











457
chr6:
chr6:
AAGGAAGAACAA
AATGTTAAGGAG
2
10
1.87
4.93E−04
exon
CLL



25975158-
25973513-
GACTTTGTTTAG
TCATCAAGTTAG




incl.




25983391
25983391
TGTGACTCTGGA
TGTGACTCTGGA











TCCA (765)
TCCA (766)











458
chr11:
chr11:
AGGAGAACACCT
AGGAGAACACCT
15
55
1.81
1.53E−04
3′ss
CLL



10876665-
10876633-
TATTTCAGCTTT
TATTTCAGAAAA









10877690
10877690
TATTTTTATGTG
GGTGTACCATAC











ATAA (767)
CTGA (768)











459
chr9:
chf9:
CTGATGAAAACT
CTGATGAAAACT
12
43
1.76
4.16E−05
3′ss
CLL



93641235-
93641235-
ACTACAAGACAC
ACTACAAGGCCC









93648127
93650030
CTTACAGGCCAG
AGACCCATGGAA











GAGA (769)
AGTG (723)











460
chr8:
chr8:
GGGGCCACCAGG
GGGGCCACCAGG
21
72
1.73
2.11E−05
3′ss
CLL



145313817-
145313817-
TTGGCCAGCGGC
TTGGCCAGGGCC









145314126
145314142
CCCCTTTCCCAG
ATGGCTGAGCAC











GGCC (770)
GCAG (771)











461
chr7:
chr7:
TGCACACGCCTC
TGCACACGCCTC
4
15
1.68
2.26E−02
3′ss
CLL



98579583-
98579583-
TCCTACAGAGTC
TCCTACAGGCAG









98580862
98580886
TCTTATGCTGGT
CCCAGCAAATCA











CCCA (772)
TCGA (773)











462
chr22:
chr22:
GAGCTGGAGAGG
GAGCTGGAGAGG
14
46
1.65
2.74E−04
3′ss
CLL



50660983-
50661021-
AAGGCGAGAGGC
AAGGCGAGGCAG









50662569
50662569
AGCTCGTCGGGA
GCACTGGTCGAC











GCAG (774)
CACT (775)











463
chr6:
chr6:
GCCCCCGTTTTC
GCCCCCGTTTTC
17
55
1.64
1.17E−04
3′ss
CLL



31936315-
31936315-
CTGCCCAGCCCT
CTGCCCAGTACC









31936399
31936462
TGTCCTCAGTGC
TGAAGCTGCGGG











ACCC (307)
AGCG (308)











464
chr7:
chr7:
CCGCCTCTGCCT
CCGCCTCTGCCT
8
26
1.58
3.53E−03
3′ss
CLL



64139714-
64139714-
TCGGATAGGTCT
TCGGATAGGAAA









64150776
64144464
GGCCCCACCCTG
GGTTGAAAGAGC











GAGT (776)
CAAC (777)











465
chr12:
chr12:
TTTCTCATATTG
TTTCTCATATTG
5
17
1.58
4.42E−03
3′ss
CLL



51174021-
51174021-
CTCAACAGTTCT
CTCAACAGGTAT









51189680
51189691
TTTTTAGGTATC
CATCTTTATCAG











ATCT (778)
AAAG (779)











466
chr11:
chr11:
AGTGGCTTTGGC
AGTGGCTTTGGC
15
46
1.55
1.99E−03
intron
CLL



126144916-
126144916-
GTCTTATGGAGG
GTCTTATGGGAT




reten-




126144918
126145221
CTTGCTTGCAGA
GGAGGACGAAGG




tion






GGGG (780)
TTGG (781)











467
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
20
60
1.54
6.97E−06
3′ss
CLL



67890660-
67890642-
GATAGATCTTCT
GATAGATCTGGC









67890765
67890765
TTTTCACATTAC
CTGAAGCACGAG











AGTG (444)
GACA (445)











468
chr1:
chr1:
GGTGACACTCAA
GGTGACACTCAA
22
65
1.52
1.10E−05
3′ss
CLL



157771381-
157771367-
CTTCACAGGTCT
CTTCACAGTGCC









157771704
157771704
CTCCCTCTAGTG
TACTGGGGCCAG











CCTA (782)
AAGC (783)











469
chr2:
chr2:
GGCAACTTCGTT
GGCAACTTCGTT
27
76
1.46
7.08E−07
3′ss
CLL



106781255-
106781240-
AATATGAGCTTT
AATATGAGGTCT









106782511
106782511
CTACTCAACAGG
ATCCAGGAAAAT











TCTA (375)
GGTG (376)











470
chr14:
chr14:
CGCTCTCCGCCT
AGGGAGACGTTC
19
54
1.46
2.09E−04
exon
CLL



75348719-
75349327-
TCCAGAAGGGGT
CCTGCCTGGGGT




skip




75352288
75352288
CTCCTTATGCCA
CTCCTTATGCCA











GGGA (208)
GGGA (209)











471
chr2:
chr2:
TTTCCATTGGGC
GAGGGCCACCAA
3
10
1.46
4.35E−02
exon
CLL



153551136-
153551136-
CAATCAAGATGC
TGGGACAAATGC




incl.




153571063
153572508
CTGGAATGATGT
CTGGAATGATGT











CGTC (784)
CGTC (785)











472
chrX:
chrX:
AGAGACAAAGAG
AGAGACAAAGAG
33
92
1.45
4.85E−06
3′ss
CLL



118759359-
118759342-
AAGAAAAACTCT
AAGAAAAATTAA









118763280
118763280
TACTGTTTTACA
CTCTGCTGTTTG











GTTA (786)
CTGC (787)











473
chr17:
chr17:
CTCACCAGCGCC
CTCACCAGCGCC
5
15
1.42
1.43E−03
exon
CLL



27238402-
27238255-
ATCGTCAGCTCT
ATCGTCAGATGG




incl.




27239499
27239499
AGGAGTTCCAGA
CAAGGTCAGCCC











GCCT (788)
CGGC (789)











474
chr12:
chr12:
ATCAGGTGCTCA
ATCAGGTGCTCA
11
30
1.37
9.13E−04
3′ss
CLL



50821692-
50821692-
TCCTGAGGTGTC
TCCTGAGGGTAA









50822699
50822717
TGTCTTTAATAC
TGCAGAGCTCTC











AGGT (790)
AGAA (791)











475
chr6:
chr6:
TCTGGCAGCCCA
TCTGGCAGCCCA
17
45
1.35
1.98E−04
3′ss
CLL



43152643-
43152643-
CGATGCTGCAAG
CGATGCTGGGAG









43153228
43153193
ATGGCATCGAGC
TCGGGCTCACGT











AGCA (792)
CCTT (793)











476
chr3:
chr3:
AGAATTTTAAGA
AGAATTTTAAGA
11
29
1.32
1.64E−03
3′ss
CLL



3186394-
3186394-
TACTTCAGATTT
TACTTCAGGTTT









3188099
3188113
TGTCTTGTAGGT
TATGGGAGAATT











TTTA (794)
GTAG (795)











477
chr7:
chr7:
CCGCCTCTGCCT
CCGCCTCTGCCT
1
4
1.32
2.43E−02
3′ss
CLL



64139714-
64139714-
TCGGATAGGCTT
TCGGATAGGAAA









64150765
64144464
TATTTAGGTCTG
GGTTGAAAGAGC











GCCC (796)
CAAC (777)











478
chr3:
chr3:
GAGCTAGTCAGA
AAATTCTTGACC
15
38
1.29
1.66E−02
exon
CLL



56606456-
56605330-
CTTTAGAGGAAA
AATCTAGGGAAA




incl.




56626997
56626997
CAGTACTGCTGG
CAGTACTGCTGG











AGCA (797)
AGCA (798)











479
chr22:
chr22:
CTTCATCTGTGG
CTTCATCTGTGG
25
61
1.25
5.02E−06
3′ss
CLL



24043032-
24037704-
ATAAGCAGGTCA
ATAAGCAGTGCA









24047615
24047615
TGTCCTCCAGGT
GGCCAAGGCCCC











TTCT (799)
CTGC (800)











480
chr17:
chr17:
CCGGAGCCCCTT
CCGGAGCCCCTT
8
20
1.22
1.07E−02
3′ss
CLL



45229302-
45229284-
CAAAAAAGACTT
CAAAAAAGTCTG









45232037
45232037
TTCGTGTTTTAC
TTGCCAGAATCG











AGTC (327)
GCCA (328)











481
chr1:
chr1:
AGTATGGGATAT
TCATTCTTATTT
8
20
1.22
2.03E−02
exon
CLL



62149218-
62149218-
TTTAAAAGATTG
CAATGCAGATTG




incl.




62152463
62160368
TTGGACCTTCAG
TTGGACCTTCAG











ATGG (801)
ATGG (802)











482
chr22:
chr22:
CTTTATCTGTGC
CTTCATCTGTGG
31
73
1.21
1.26E−05
exon
CLL



24037704-
24037704-
ATGAACAGTGCA
ATAAGCAGTGCA




incl.




24042912
24047615
GGCCAAGGCCCC
GGCCAAGGCCCC











CTGC (803)
CTGC (800)











483
chr7:
chr7:
AAGTCGTCCTCT
AGAGAGAAACAT
18
42
118
2.78E−02
exon
CLL



104844232-
104844232-
TCAGAAAGGCCG
CCGAAAAAGCCG




incl.




104909252
105029094
GAGCCTCAACAG
GAGCCTCAACAG











AAAG (804)
AAAG (805)











484
chr2:
chr2:
TGGGCTACCTTA
TGGGCTACCTTA
23
53
1.17
3.28E−02
exon
CLL



85779690-
85779104-
ACCCTGGGGTAT
ACCCTGGGGATT




incl.




85780061
85780061
TTACACAGAGTC
TTTGACCCTCGT











GGCG (806)
GTGG (807)











485
chr1:
chr1:
GACTGCCCTAAA
GACTGCCCTAAA
10
23
1.13
4.92E−03
3′ss
CLL



52902647-
52902635-
AGGAAAAGTTTA
AGGAAAAGACTA









52903891
52903891
CTGTTTAGACTA
AAGAAGAAAGAC











AAGA (808)
AGTG (809)











486
chr3:
chr3:
TGATAGTTGGAG
TGATAGTTGGAG
11
25
1.12
3.47E−03
3′ss
CLL



179065598-
179065598-
CGGAGACTCATA
CGGAGACTTAGC









179066635
179066632
ATGGCAGAACCT
ATAATGGCAGAA











GTTT (810)
CCTG (811)











487
chr1:
chr1:
TCATTCTTATTT
TCATTCTTATTT
5
12
112
3.19E−02
exon
CLL



62152593-
62149218-
CAATGCAGAGAC
CAATGCAGATTG




incl.




62160368
62160368
AGGGTCTTGCTC
TTGGACCTTCAG











TGTT (812)
ATGG (802)











488
chr19:
chr19:
TGACGGTGCCAC
TGACGGTGCCAC
30
65
1.09
4.13E−02
exon
CLL



53935281-
53935281-
CGCGGCGCTTTT
CGCGGCGCAGAG




incl.




53936832
53945048
CTCCCTTAGATG
GAGTCTGCAATG











CCTT (813)
CCGA (814)











489
chr19:
chr19:
GCAGTGGCTGGA
GCAGTGGCTGGA
42
85
1.00
4.02E−05
3′ss
CLL



19414656-
19414721-
GATCAAAGTTTC
GATCAAAGAGAG









19416657
19416657
ACCCCCAGAGGG
AGTGTGCCTATT











AGCC (815)
GACT (816)











490
chrX:
chrX:
GGACGATGGGGA
GGACGATGGGGA
3
7
1.00
8.68E−03
3′ss
CLL



47103949-
47103949-
TGAGAAAGATGA
TGAGAAAGAAGA









47104083
47104080
CGAGGAGGATAA
TGACGAGGAGGA











AGAT(817)
TAAA(818)











491
chr5:
chr5:
ACTCTTATGCAG
ACTCTTATGCAG
24
48
0.97
7.63E−03
3′ss
CLL



1579599-
1581810-
TCCCCATGGACT
TCCCCATGAGGA









1585098
1585098
GAACCATCAAGA
GATCCTAGTCTC











CACC(819)
ACCA(531)











492
chr17:
chr17:
GACCCATGCATC
GACCCATGCATC
47
93
0.97
2.22E−02
3′ss
CLL



73587327-
73587327-
CTCCTGTGCTCC
CTCCTGTGTGGG









73587681
73587696
TCCCACTGCAGT
CACAGTGGCTCA











GGGC(820)
GGGA(821)











493
chr18:
chr18:
CCAAGTTTTGTG
CCAAGTTTTGTG
38
75
0.96
7.90E−03
3′ss
CLL



224200-
224179-
AAAGAAAGTGTA
AAAGAAAGAACA









224923
224923
TGTTTTGTTCAC
TCAGATACCAAA











GACA(116)
CCTA(117)











494
chr16:
chr16:
CATCAAGCAGCT
CATCAAGCAGCT
10
20
0.93
2.86E−02
3′ss
CLL



57473207-
57473246-
GTTGCAATGTTT
GTTGCAATCTGC









57474683
57474683
AGTCCCAGGAAG
CCACAAAGAATC











CACC(822)
CAGC(823)











495
chr7:
chr7:
TGAGAGTCTTCA
TGAGAGTCTTCA
45
86
0.92
7.69E−08
3′ss
CLL



99943591-
99943591-
GTTACTAGTTTG
GTTACTAGAGGC









99947339
99947421
TCTTTCCTAGAT
GGATTTCCCTGA











CCAG(420)
CTGA(421)











496
chr12:
chr12:
CAATCATTGACA
CAATCATTGACA
29
54
0.87
3.27E−02
3′ss
CLL



47599928-
47599852-
ATATTATGACCC
ATATTATGGAAC









47600293
47600293
TGCATGTGATGG
TGACTCAGCGCA











ATCA(824)
AGAA(825)











497
chr9:
chf9:
GGGACACTGTGC
GGGACACTGTGC
43
72
0.73
1.74E−02
3′ss
CLL



140633231-
140633231-
CGAATGAACTTG
CGAATGAACAGC









140637822
140637843
CTTGCCTTTTGT
TGCAGTATCTCG











TTTA(826)
GAAG(827)











498
chr19:
chr19:
TCAGGGGGCGCG
TCGAGCCAGGCT
to
17
0.71
2.37E−02
exon
CLL



17654242-
17654440-
TGCTGAAGGAGC
GCAAAAAGGAGC




skip




17657494
17657494
TGCCTGAGTTCG
TGCCTGAGTTCG











AGGG(828)
AGGG(829)











499
chr6:
chr6:
CTACAACCAGAG
CTACAACCAGAG
57
92
0.68
2.50E−03
3′ss
CLL



29691704-
29691704-
CGAGGCTGGGTC
CGAGGCTGGGAA









29691949
29691966
TCACACCCTCCA
TGAATGGCTGCG











GGGA(830)
ACAT(831)











500
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
54
87
0.68
4.59E−02
3′ss
CLL



30310151-
30310133-
ATTTGAATCTCT
ATTTGAATAATC









30310420
30310420
TTCTCTCCCTTC
TTATCTTGGCTT











AGAA(479)
TGGA(480)











501
chr4:
chr4:
TCCAACAAGCAC
TCCAACAAGCAC
55
87
0.65
1.64E−04
3′ss
CLL



17806394-
17806379-
CTCTGAAGTCTT
CTCTGAAGGTTA









17806729
17806729
CTCATTCACAGG
AGGCTACCTTTC











TTAA(832)
CAGA(833)











502
chr9:
chr9:
CACCACAAAATC
CACCACAAAATC
41
65
0.65
4.07E−03
3′ss
CLL



140622981-
140622981-
ACAGACAGCTTG
ACAGACAGCAGC









140637822
140637843
CTTGCCTTTTGT
TGCAGTATCTCG











TTTA(458)
GAAG(459)











503
chr1:
chr1:
GAATCCGTATCT
GAATCCGTATCT
45
70
0.63
4.59E−02
3′ss
CLL



155278756-
155278756-
GGGAACAGAGCC
GGGAACAGAATG









155279833
155279854
CTTTGCTCCTCC
AACGGAGACCAG











CTCA(432)
AATT(433)











504
chr17:
chr17:
GTTCCCGAGGCT
GTTCCCGAGGCT
60
90
0.58
8.49E−05
3′ss
CLL



40690773-
40690773-
GTCACCAGGGTG
GTCACCAGTGGA









40692967
40695045
TTCCCTCAGGTC
TACTGAGGCTGT











AATG (834)
GTGG (835)











505
chr12:
chr12:
ATTTCCAGAGGA
ATTTCCAGAGGA
51
76
0.57
1.45E−05
3′ss
CLL



95660408-
95660408-
TTTACACTTTTG
TTTACACTGGTC









95663814
95663826
CTTGACAGGGTC
AGTGCTGCTTGC











AGTG (462)
CCAT (463)











506
chr3:
chr3:
CCAGATCAACAC
CCAGATCAACAC
44
65
0.55
2.77E−02
3′ss
CLL



133371473-
133371458-
AATTGATAGTCG
AATTGATAATGT









133372188
133372188
TACTCTTTCAGA
CAGCAATATTTC











TGTC (836)
CAAC (837)











507
chr19:
chr19:
CGTCCTGCCCCC
CGTCCTGCCCCC
67
94
0.48
2.30E−02
3′ss
CLL



7075116-
7075116-
AACTGCCGCTCT
AACTGCCGCCTC









7075665
7075686
GTCTTCCCTGTT
TCAGCGAGAAGG











CCCA (838)
ACAC (839)











508
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
53
74
0.47
2.22E−03
3′ss
CLL



75554088-
75554088-
TGCTCCAGTGGT
TGCTCCAGGTTC









75554298
75554313
TTCTCCCACAGG
CCGGCCCCCAAG











TTCC (466)
TCGC (467)











509
chr19:
chr19:
TGCAGGGGGAGC
TGCAGGGGGAGC
48
66
0.45
6.62E−03
3′ss
CLL



11558433-
11558433-
AGCCCAAGGAGG
AGCCCAAGCCGG









11558507
11558537
CCCCACCGCCAC
CCAGCCCTGCTG











TGTC (840)
AGGA (841)











510
chr1:
chr1:
GACTGCCCTAAA
GACTGCCCTAAA
55
74
0.42
8.74E−03
3′ss
CLL



52902650-
52902635-
AGGAAAAGCAGT
AGGAAAAGACTA









52903891
52903891
TTACTGTTTAGA
AAGAAGAAAGAC











CTAA (842)
AGTG (809)











511
chr17:
chr17:
CTATGAGGCCAT
GTTCCCGAGGCT
68
87
0.35
1.45E−03
exon
CLL



40693224-
40690773-
GACTGCAGTGGA
GTCACCAGTGGA




incl.




40695045
40695045
TACTGAGGCTGT
TACTGAGGCTGT











GTGG (843)
GTGG (835)











512
chr5:
chr5:
CTTCTCAAGATC
CTTCTCAAGATC
70
86
0.29
2.73E−02
3′ss
CLL



139865317-
139865317-
AGTCTCAGGTGC
AGTCTCAGGAAC









139866542
139866590
CACGTGTGCCAA
CTGACAGAACTT











CGCA (844)
CACA (845)











513
chr6:
chr6:
ACCTTAACAAGA
AATCACTAGGAA
58
71
0.29
1.38E−02
exon
CLL



127636041-
127636041-
TTTATGAGACTT
CTCCAGAGACTT




incl.




127637594
127648146
CCTTTAATAAGT
CCTTTAATAAGT











GTTG (846)
GTTG (847)











514
chr4:
chr4:
ACTGGGCTTCCA
ACTGGGCTTCCA
60
72
0.26
4.54E−02
exon
CLL



54266006-
54266006-
CCGAGCAGAAAC
CCGAGCAGGAGA




incl.




54280781
54292038
AGCACTTCTTCT
TTACCTGGGGCA











CAGT (848)
ATTG (849)











515
chr9:
chf9:
CTGAAGACGGGA
CTGAAGACGGGA
87
92
0.08
2.80E−02
3′ss
CLL



130566979-
130566979-
TTCTTTAGCTCT
TTCTTTAGGTTC









130569251
130569270
CCCCACCTGGTG
GGGAGCGGATCC











CAGG (850)
GCAT (851)











516
chr17:
chr17:
ATCTCAGGAGCA
CCCACCCCTTCA
93
98
0.07
4.18E−03
5′ss
CLL



72759659-
72760785-
CCTGAATGGTCC
CCCTGCAGGTCC









72763074
72763074
CCTGCCTGTGCC
CCTGCCTGTGCC











CTTC (852)
CTTC (853)











517
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
0
72
6.19
1.51E−10
3′ss
Mel.



109102364-
109102364-
TCTATAAAATTT
TCTATAAAATAC









109102954
109102966
ACCCCCAGATAC
AGCTGGCTGAAA











AGCT (1)
TAAC (2)











518
chr19:
chr19:
GGCCCTTTTGTC
GGCCCTTTTGTC
0
72
6.19
7.67E−09
3′ss
Mel.



57908542-
57908542-
CTCACTAGCATT
CTCACTAGGTTC









57909780
57909797
TCTGTTCTGACA
TTGGCATGGAGC











GGTT (7)
TGAG (8)











519
chr2:
chr2:
TGACCACGGAGT
TGACCACGGAGT
0
59
5.91
1.12E−08
3′ss
Mel.



232196609-
232196609-
ACCTGGGGCCCT
ACCTGGGGATCA









232209660
232209686
TTTTTCTCTTTC
TGACCAACACGG











CTTC (37)
GGAA (38)











520
chr1:
chr1:
CAAGTATATGAC
CAAGTATATGAC
0
56
5.83
3.98E−05
3′ss
Mel.



245246990-
245246990-
TGAAGAAGATCC
TGAAGAAGGTGA









245288006
245250546
TGAATTCCAGCA
GCCTTTTTCTCA











AAAC (21)
AGAG (22)











521
chr11:
chr11:
GGCCACACGCCT
GGCCACACGCCT
0
54
5.78
1.58E−06
3′ss
Mel.



65635911-
65635892-
CTGCCAAGCCCC
CTGCCAAGACAT









65635980
65635980
TCTCCCCTGGCA
TGATGAGTGTGA











CAGA (854)
GTCT (855)











522
chr3:
chr3:
TGCAGTTTGGTC
TGCAGTTTGGTC
0
49
5.64
5.19E−07
3′ss
Mel.



9960293-
9960293-
AGTCTGTGCCTT
AGTCTGTGGGCT









9962150
9962174
CCTCACCCCTCT
CTGTGGTATATG











CCTC (23)
ACTG (24)











523
chr3:
chr3:
GAGTACGAGGTC
GAGTACGAGGTC
0
48
5.61
2.52E−15
3′ss
Mel.



48457878-
48457860-
TCCAGCAGCCTG
TCCAGCAGCCTC









48459319
48459319
CCCTGTGCCTAC
GTGTGCATCACC











AGCC (856)
GGGG (857)











524
chr1O:
chr1O:
TACCTCTGGTTC
TACCTCTGGTTC
0
47
5.58
5.54E−06
3′ss
Mel.



99214556-
99214556-
CTGTGCAGTCTT
CTGTGCAGTTCT









99215395
99215416
CGCCCCTCTTTT
GTGGCACTTGCC











CTTA (13)
CTGG (14)











525
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
45
5.52
3.06E−06
3′ss
Mel.



101458310-
101458296-
CTAATCAATTTT
CTAATCAAGGGA









101460665
101460665
CTGCCTATAGGG
AGGAAGATCTAT











GAAG (25)
GAAC (26)











526
chr9:
chr9:
AGCGCATCGCAG
AGCGCATCGCAG
0
45
5.52
1.42E−03
3′ss
Mel.



90582559-
90582574-
CTTCCAAGTACT
CTTCCAAGGCTC









90584108
90584108
TCTTCACAGCTC
TCCTCCATCAGT











CCCT (858)
ACTT (859)











527
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
44
5.49
1.90E−07
3′ss
Mel.



179835004-
179834989-
TAAACGAGTTTT
TAAACGAGGTAT









179846373
179846373
ATCATTTACAGG
GTGACGCATTCC











TATG (53)
CAGA (54)











528
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
41
5.39
4.30E−08
3′ss
Mel.



74358911-
74358911-
AACCAGAGTGTT
AACCAGAGCTCC









74360478
74360499
GTCTTTTCTCCC
TGGTACAGTTTG











CCCA (61)
TTCA (62)











529
chr11:
chr11:
TGGGCAGCCCCC
TGGGCAGCCCCC
0
39
5.32
2.61E−02
3′ss
Mel.



117167925-
117167677-
CGCAGACGTTGG
CGCAGACGCTCA









117186250
117186250
TTTTTCAGCAGA
ACATCCTGGTGG











CCTG (860)
ATAC (861)











530
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
36
5.21
6.58E−07
3′ss
Mel.



62701988-
62701988-
ACACACAGCCCT
ACACACAGGTGC









62703210
62703222
GTTCACAGGTGC
AGACCCGCAGCT











AGAC (29)
CTGA (30)











531
chr18:
chr18:
AGAAAGAGCATA
AGAAAGAGCATA
0
33
5.09
6.82E−09
3′ss
Mel.



33605641-
33573263-
AATTGGAAATAT
AATTGGAAGAGT









33606862
33606862
TGGACATGGGCG
ACAAGCGCAAGC











TATC (91)
TAGC (92)











532
chr3:
chr3:
AACCAAGAGGAC
AACCAAGAGGAC
0
32
5.04
1.83E−02
3′ss
Mel.



52283338-
52283338-
CCACACAGGATG
CCACACAGGTTC









52283671
52283685
GTCTTCACAGGT
TCAAAGCTGGCC











TCTC (862)
CAGA (863)











533
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
32
5.04
6.82E−09
3′ss
Mel.



125759640-
125759640-
TCCTAAAGCCTC
TCCTAAAGATAA









125760854
125760875
TCTCTTTCTTTG
AGTCCTGTTTAT











TTTA (67)
GACC (68)











534
chr12:
chr12:
AATATTGCTTTA
AATATTGCTTTA
0
31
5.00
9.14E−06
3′ss
Mel.



116413154-
116413118-
CCAAACAGGGAC
CCAAACAGGTCA









116413319
116413319
CCCTTCCCCTTC
CGGAGGAGTAAA











CCCA (77)
GTAT (78)











535
chr18:
chr18:
TTGGACCGGAAA
TTGGACCGGAAA
1
62
4.98
1.13E−06
3′ss
Mel.



683395-
683380-
AGACTTTGAGTC
AGACTTTGATGA









685920
685920
TCTTTTTGCAGA
TGGATGCCAACC











TGAT (15)
AGCG (16)











536
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
0
29
4.91
8.06E−03
3′ss
Mel.



212515622-
212515622-
TACAACAGGTTT
TACAACAGCTCC









212519131
212519144
CTTTTAAAGCTC
TGGAGCTTTTTG











CTGG (65)
ATAG (66)











537
chr1:
chr1:
CTCAGAGCCAGG
CTCAGAGCCAGG
0
29
4.91
3.06E−05
3′ss
Mel.



35871069-
35871069-
CTGTAGAGATGT
CTGTAGAGTCCG









35873587
35873608
TTTCTACCTTTC
CTCTATCAAGCT











CACA (105)
GAAG (106)











538
chrX:
chrX:
GTCTTGAGAATT
ACTTCCTTAGTG
0
29
4.91
1.16E−06
5′ss
Mel.



47059943-
47059013-
GGAAGCAGGTGG
GTTTCCAGGTGG









47060292
47060292
TGGTGCTCACCA
TGGTGCTCACCA











ACAC (113)
ACAC (112)











539
chr2:
chr2:
AAATTTAACATT
AAATTTAACATT
0
28
4.86
3.75E−06
3′ss
Mel.



24207701-
24207701-
ACTCATAGTTTT
ACTCATAGAGTA









24222524
24222541
TGCTGTTTTACA
AGCCATATCAAA











GAGT (546)
GACT (547)











540
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
0
28
4.86
8.03E−04
3′ss
Mel.



869519-
865696-
CTCTCTGGTTTC
CTCTCTGGGGAA









870587
870587
TTTCAGGGCCTG
GGTGAAGAAGGA











CCAT (128)
GCTG (129)











541
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
27
4.81
4.86E−06
3′ss
Mel.



34144042-
34144042-
ACGGAGAGGCTC
ACGGAGAGGTAC









34144725
34144743
CCCTCCCACCCC
TGAGGACAAATC











AGGT (49)
AGTT (50)











542
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
27
4.81
1.72E−04
3′ss
Mel.



97285513-
97285499-
GTCAACAGAGTT
GTCAACAGGACT









97297048
97297048
TCCCTTATAGGA
GGCTGGACAATG











CTGG (9)
GCCC (10)











543
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
1
54
4.78
1.18E−09
3′ss
Mel.



9728842-
9728855-
GTCCCGTGGGAA
GTCCCGTGGGTT









9730107
9730107
CCAATCTGCCCT
TTTTTCCAGGGA











TTTG (160)
ACCA (161)











544
chr15:
chr15:
ATATTCCTTTTA
ATATTCCTTTTA
0
25
4.70
3.65E−06
3′ss
Mel.



49420970-
49420957-
TTTCTAAGTCTT
TTTCTAAGGAGT









49421673
49421673
TTGTCTTAGGAG
TAAACATAGATG











TTAA (864)
TAGC (865)











545
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
1
49
4.64
6.42E−06
3′ss
Mel.



105601825-
105601807-
TAGCAATGATGT
TAGCAATGAGCA









105601935
105601935
CTGTTTATTTTT
TGACCTCTCAAT











AGAG (41)
GGCA (42)











546
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
0
24
4.64
2.35E−03
3′ss
Mel.



75356052-
75356052-
GGAGAAAGCCTT
GGAGAAAGCTGT









75356580
75356599
TGATTGTCTTTT
TGGAGACACAGT











CAGC (89)
TGCA (90)











547
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
0
23
4.58
4.56E−05
3′ss
Mel.



4104212-
4104212-
ACAGCTAATTCT
ACAGCTAAGCAA









4104471
4104492
CTTTCCTCTGTC
GCACTGAGCGAG











TTCA (69)
GTGA (70)











548
chr15:
chr15:
GAAACCAACTAA
GAAACCAACTAA
0
23
4.58
2.75E−04
3′ss
Mel.



59209219-
59209198-
AGGCAAAGCCCA
AGGCAAAGGTAA









59224554
59224554
TTTTCCTTCTTT
AAAACATGAAGC











CGCA (101)
AGAT (102)











549
chr22:
chr22:
CTGGGAGGTGGC
CTGGGAGGTGGC
0
23
4.58
1.03E−06
3′ss
Mel.



19044699-
19044675-
ATTCAAAGCCCC
ATTCAAAGGCTC









19050714
19050714
ACCTTTTGTCTC
TTCAGAGGTGTT











CCCA (45)
CCTG (46)











550
chr3:
chr3:
CACTGCTGGGAG
CACTGCTGGGAG
0
23
4.58
5.29E−10
3′ss
Mel.



129284872-
129284860-
AGTGGAAGTTGC
AGTGGAAGATTC









129285369
129285369
TTCCACAGATTC
CTGAGAGCTGCC











CTGA (524)
GGCC (525)











551
chr9:
chr9:
GGTCCTGAACGC
GGTCCTGAACGC
0
23
4.58
1.89E−04
3′ss
Mel.



138903859-
138903870-
TGTGAAATAACT
TGTGAAATTGTA









138905044
138905044
TCGCCCCCAGCT
CTGTCAGAACTT











TCAA (866)
CGCC (867)











552
chr6:
chr6:
TGGAGCAGTATG
TGGAGCAGTATG
0
22
4.52
8.93E−03
3′ss
Mel.



35255622-
35255622-
CCAGCAAGACTT
CCAGCAAGGTTC









35258029
35258042
TTCCCCCAGGTT
TTCATGACAGCC











CTTC (868)
AGAT (869)











553
chr8:
chr8:
TCGTGCAGACCC
TCGTGCAGACCC
0
22
4.52
3.21E−11
3′ss
Mel.



28625893-
28625839-
TGGAGAAGATCT
TGGAGAAGCATG









28627405
28627405
CACAGATGTGCA
GCTTCAGTGATA











GTCT (870)
TTAA (871)











554
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
2
67
4.5
2.74E−12
3′ss
Mel.



10723474-
10723474-
TGAGACCGCTTG
TGAGACCGGTGC









10724788
10724802
TTTTCTGCAGGT
AGGCCTGGGGTA











GCAG (95)
GTCT (96)











555
chr4:
chr4:
GTGCCAACGAGG
GTGCCAACGAGG
2
65
4.46
9.90E−07
3′ss
Mel.



184577127-
184577114-
ACCAGGAGTTCT
ACCAGGAGATGG









184580081
184580081
TTATTTCAGATG
AACTAGAAGCAT











GAAC (734)
TACG (735)











556
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
21
4.46
4.84E−04
3′ss
Mel.



39064137-
39064137-
TGCATTCTCATC
TGCATTCTTTGG









39066874
39066888
TCGCCCACAGTT
ATCGATCAACCC











GGAT (140)
GGGA (141)











557
chr9:
chr9:
TTGAAGCTCAGT
TTGAAGCTCAGT
0
21
4.46
3.30E−03
3′ss
Mel.



37501841-
37501841-
GAGAAAAGTTCT
GAGAAAAGGATG









37503015
37503039
TCTGTTTATGTC
ATGGAGATAGCC











TTCC (872)
AAAG (873)











558
chr14:
chr14:
CAGTTATAAACT
CAGTTATAAACT
0
20
4.39
2.55E−03
3′ss
Mel.



71059726-
71059705-
CTAGAGTGAGTT
CTAGAGTGCTTA









71060012
71060012
TATTTTCCTTTT
CTGCAGTGCATG











ACAA (79)
GTAT (80)











559
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
20
4.39
2.74E−12
3′ss
Mel.



71198039-
71198039-
TTGTGAAATCAT
TTGTGAAAGTTT









71199162
71199138
TACTTCTAGATG
TGATTCATGGAT











ATGC (31)
TCAC (32)











560
chr9:
chr9:
CGCCCTGACACA
CGCCCTGACACA
0
20
4.39
1.26E−04
3′ss
Mel.



35608506-
35608506-
CAATCAGGACTT
CAATCAGGGCTC









35608842
35608858
CTCTATCTACAG
TGTTGCAAGAGG











GCTC (874)
GGGT (875)











561
chrX:
chrX:
ACTTCCTTAGTG
ACTTCCTTAGTG
0
20
4.39
2.32E−03
3′ss
Mel.



47059013-
47059013-
GTTTCCAGGTTG
GTTTCCAGGTGG









47059808
47060292
CCAGGGCACTGC
TGGTGCTCACCA











AGCT (111)
ACAC (112)











562
chr12:
chr12:
CTTGGAGCTGAC
CTTGGAGCTGAC
4
96
4.28
5.10E−13
3′ss
Mel.



107378993-
107379003-
GCCGACGGGGAA
GCCGACGGTTTA









107380746
107380746
CTGACAAGATCA
TTGCAGGGAACT











CATT (130)
GACA (131)











563
chr10:
chr10:
TTGCTGGCCATC
TTGCTGGCCATC
0
18
4.25
1.13E−14
3′ss
Mel.



133782836-
133782073-
GGATTGGGCCCT
GGATTGGGGATC









133784141
133784141
TCGTTTCAGGAT
TATATTGGAAGG











GGAT (876)
CGTC (877)











564
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
0
18
4.25
6.04E−04
3′ss
Mel.



64877395-
64877395-
ACGTGCAGTACC
ACGTGCAGGTGG









64877934
64877953
TCTTTTTACCAC
GGCTCCTGTACG











CAGG (167)
AAGA (168)











565
chr21:
chr21:
ATCATAGCCCAC
ATCATAGCCCAC
1
35
4.17
1.72E−04
3′ss
Mel.



37416267-
37416254-
ATGTCCAGTTTT
ATGTCCAGGTAA









37417879
37417879
TCTTTCTAGGTA
AAGCAGCGTTTA











AAAG (695)
ATGA (696)











566
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
1
34
4.13
1.03E−06
3′ss
Mel.



25213229-
25213229-
AAAACCAGCCTT
AAAACCAGGCTC









25219533
25219457
CCCCTAGGTCTT
CATCTACTCTTT











CAGA (230)
GAAG (231)











567
chr17:
chr17:
TACTGAAATGTG
TACTGAAATGTG
0
16
4.09
5.46E−04
3′ss
Mel.



34942628-
34942628-
ATGAACATATCC
ATGAACATATCC









34943454
34943426
AGGTAATCGAGA
AGAAGCTTGGAA











GACC (124)
GCTG (125)











568
chr2:
chr2:
CCATTCGAGAGC
CCATTCGAGAGC
0
16
4.09
2.25E−03
3′ss
Mel.



219610954-
219610954-
ATCAGAAGATTG
ATCAGAAGCTAA









219611752
219611725
GGAGGAAGGACC
ACCATTTCCCAG











GGCT (878)
GCTC (879)











569
chr10:
chr10:
TCTTGCCAGAGC
TCTTGCCAGAGC
0
15
4.00
9.94E−07
3′ss
Mel.



99219232-
99219283-
TGCCCACGCTCT
TGCCCACGCTTC









99219415
99219415
CCACCCTCAGCT
TTTCCTTGCTGC











GCCT (587)
TGGA (588)











570
chr11:
chr11:
AGATCGCCTGGC
AGATCGCCTGGC
0
15
4.00
9.65E−05
3′ss
Mel.



3697619-
3697606-
TCAGTCAGTTTT
TCAGTCAGACAT









3697738
3697738
TCTCTCTAGACA
GGCCAAACGTGT











TGGC (187)
AGCC (188)











571
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
15
4.00
4.00E−05
3′ss
Mel.



62648919-
62648919-
CCTGGCGGCCCC
CCTGGCGGGTCT









62649352
62649364
CATTTCAGGTCT
GAAGGGGCGTCT











GAAG (165)
CGAT (166)











572
chr1:
chr1:
TCAGGAGCAGAG
CTCAGGGAAGGG
0
15
4.00
2.96E−02
5′ss
Mel.



113195986-
113192091-
AGGAAAAGTGCA
GCAGCACATGCA









113196219
113196219
TTTGCCCAGTAT
TTTGCCCAGTAT











AACA (880)
AACA (881)











573
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
0
15
4.00
5.55E−03
3′ss
Mel.



52880319-
52880319-
AGGAGAAGTCTG
AGGAGAAGCCCC









52880412
52880433
ACCAGTCTTTTC
TCCCCTCGCCGA











TACA (55)
GAAA (56)











574
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
1
30
3.95
6.03E−06
exon
Mel.



25212299-
25207356-
ATTTGAAAGTGT
AACCAAGAGTGT




incl.




25213078
25213078
CAGTTGTACCCG
CAGTTGTACCCG











AGGC (164)
AGGC (145)











575
chr11:
chr11:
TGCAGCTGGCCC
TGCAGCTGGCCC
0
14
3.91
1.39E−07
3′ss
Mel.



64002365-
64002365-
CCGCCCAGGTCT
CCGCCCAGGCCC









64002911
64002929
TTTCTCTCCCAC
CTGTCTCCCAGC











AGGC (638)
CTGA (639)











576
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
0
14
3.91
1.83E−03
3′ss
Mel.



113346629-
113346629-
TGCCCTGGATTT
TGCCCTGGGTCA









113348840
113348855
TGCCCGAACAGG
GTTGACTGGCGG











TCAG (71)
CTAT (72)











577
chr17:
chr17:
CCAAGCTGGTGT
CCAAGCTGGTGT
0
14
3.91
1.08E−03
3′ss
Mel.



78188582-
78188564-
GCGCACAGGCCT
GCGCACAGGCAT









78188831
78188831
CTCTTCCCGCCC
CATCGGGAAGAA











AGGC (73)
GCAC (74)











578
chr2:
chr2:
GTGTGGCAAGTA
GTGTGGCAAGTA
0
14
3.91
1.45E−02
3′ss
Mel.



85848702-
85848702-
CTTTCAAGTATC
CTTTCAAGGCCG









85850728
85850768
TGCCCTTCTATT
GGGTTTGAAGTC











ACAG (882)
TCAC (883)











579
chr12:
chr12:
AAAATCATTGAT
AAAATCATTGAT
0
13
3.81
1.44E−03
3′ss
Mel.



29450133-
29450133-
TCCCTTGAAATT
TCCCTTGAGTGG









29460566
29460590
CTCTTTACTCTA
TTAGACGATGCT











CCTT (884)
ATTA (885)











580
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
0
13
3.81
2.75E−04
3′ss
Mel.



23237380-
23237380-
TGCTGCATTTTG
TGCTGCATGTAC









23238985
23238999
TATTTTCCAGGT
AGTCTTTGCCCG











ACAG (122)
CTGC (123)











581
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
13
3.81
5.09E−08
3′ss
Mel.



36627480-
36627512-
GAACCCAGTATT
GAACCCAGAGAG









36629198
36629198
TCCAGGACCAAG
CAGTATCTTTAT











TGAG (199)
TGAG (200)











582
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
12
3.70
4.53E−04
3′ss
Mel.



14031735-
14031735-
TCACCAAGCCTC
TCACCAAGGTGC









14034130
14034145
GTCCTCCCCAGG
CGCCTGCCCCTG











TGCC (59)
TCAA (60)











583
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
12
3.70
9.65E−05
3′ss
Mel.



35282126-
35282104-
GGGCTACATCCC
GGGCTACATACC









35284762
35284762
CTTGGTTCTCTG
ATCTGCCAGCAT











TTAC (35)
GACT (36)











584
chr22:
chr22:
TGCTCAGAGGTG
TGCTCAGAGGTG
0
12
3.70
8.43E−07
3′ss
Mel.



19948812-
19948812-
CTTTGAAGCCCA
CTTTGAAGATGC









19950181
19950049
TCCACAACCTGC
CGGAGGCCCCGC











TCAT (886)
CTCT (887)











585
chr2:
chr2:
CAAGATAGATAT
CAAGATAGATAT
0
12
3.70
3.94E−03
3′ss
Mel.



170669034-
170669016-
TATAGCAGGTGG
TATAGCAGAACT









170671986
170671986
CTTTTGTTTTAC
TCGATATGACCT











AGAA (99)
GCCA (100)











586
chr15:
chr15:
GCCTCACTGAGC
GCCTCACTGAGC
2
37
3.66
8.44E−08
exon
Mel.



25207356-
25207356-
AACCAAGAGTAG
AACCAAGAGTGT




incl.




25212175
25213078
TGACTTGTCAGG
CAGTTGTACCCG











AGGA (144)
AGGC (145)











587
chr11:
chr11:
CCACGGCCACGG
CCACGGCCACGG
4
60
3.61
3.80E−03
3′ss
Mel.



8704812-
8704812-
CCGCATAGCTTT
CCGCATAGGCAA









8705536
8705552
GTATTCCTGCAG
GCACCGGAAGCA











GCAA (888)
CCCC (889)











588
chr11:
chr11:
CATGCCGGGGCC
CATGCCGGGGCC
0
11
3.58
1.83E−02
3′ss
Mel.



11988666-
11988645-
AGAGGATGGCTC
AGAGGATGCTCT









11989941
11989941
TTTCCACCTGTC
GCACCCGGGACA











TGCA (890)
GTGA (891)











589
chr16:
chr16:
GGCGAAGCAAGA
GGCGAAGCAAGA
0
11
3.58
1.88E−02
3′ss
Mel.



19838459-
19838459-
ACAAAAAGTATT
ACAAAAAGTGAA









19843229
19867808
TTCTTCTAGGAT
ATGCAAAATGGA











GGAA (892)
GGAC (893)











590
chr1:
chr1:
GGCTCCCATTCT
GGCTCCCATTCT
0
11
3.58
2.42E−03
3′ss
Mel.



155630724-
155630704-
GGTTAAAGAGTG
GGTTAAAGGCCA









155631097
155631097
TTCTCATTTCCA
GTCTGCCATCCA











ATAG (195)
TCCA (196)











591
chr1:
chr1:
GAAGAACAGGAT
GAAGAACAGGAT
0
11
3.58
1.74E−02
3′ss
Mel.



219366593-
219366593-
ATTAATAGTATG
ATTAATAGGAGG









219383856
219383873
TTTTTGTTTTTA
ATTCTCTATGGG











GGAG (894)
AGGA (895)











592
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
0
10
3.46
2.28E−04
3′ss
Mel.



5595521-
5595508-
AAGAGAGATTTT
AAGAGAGAAGCT









5598803
5598803
GGTAAACAGAGC
CCAAGAGTCAGG











TCCA (138)
ATCG (139)











593
chr5:
chr5:
CAATTCAGTAGA
AGGTCTTCCTGG
0
10
3.46
2.42E−02
5′ss
Mel.



462644-
462422-
TTCACCCTCAAC
ACCTGGAGCAAC









464404
464404
ATCTGAATGAAT
ATCTGAATGAAT











TGAT (896)
TGAT (897)











594
chr9:
chr9:
GGGAGATGGATA
GGGAGATGGATA
3
41
3.39
1.97E−10
3′ss
Mel.



35813153-
35813142-
CCGACTTGCTCA
CCGACTTGTGAT









35813262
35813262
ATTTCAGTGATC
CAACGATGGGAA











AACG (146)
GCTG (147)











595
chr1:
chr1:
AGAGGGCACGGG
AGAGGGCACGGG
2
29
3.32
1.42E−03
3′ss
Mel.



205240383-
205240383-
ACATCCAGCCCC
ACATCCAGGAGG









205240923
205240940
TCTGCCCCTGCA
CCGTGGAGTCCT











GGAG (898)
GCCT (899)











596
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
0
9
3.32
6.24E−03
3′ss
Mel.



125442465-
125442465-
TTGCCAGACCTT
TTGCCAGAGGAA









125445146
125445158
TTCTATAGGGAA
TCAAAGACTCCA











TCAA (150)
TCTG (151)











597
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
0
9
3.32
3.79E−04
3′ss
Mel.



71939542-
71939542-
TGCCTCAGTCAC
TGCCTCAGATGG









71939690
71939770
TTTACAGCTGCA
GGAGGATGAGAA











TCGT (47)
GCCC (48)











598
chr16:
chr16:
AGATGATTGAGG
AGATGATTGAGG
0
9
3.32
1.06E−02
3′ss
Mel.



70292147-
70292120-
CAGCCAAGCTCT
CAGCCAAGGCCG









70292882
70292882
TTTCTGTCTTCT
TCTATACCCAGG











TGGT (900)
ATTG (901)











599
chr2:
chr2:
GAGGAGCCACAC
GAGGAGCCACAC
0
9
3.32
2.20E−02
3′ss
Mel.



220044485-
220044485-
TCTGACAGATAC
TCTGACAGTGAG









220044888
220044831
CTGGCTGAGAGC
GGTGCGGGGTCA











TGGC (107)
GGCG (108)











600
chr3:
chr3:
GCTGCTCTCTTC
GCTGCTCTCTTC
0
9
3.32
2.87E−06
3′ss
Mel.



45043100-
45043100-
AATACAAGTGCT
AATACAAGGATA









45046767
45046782
TCTGCTTCCAGG
CCAAGGGTTCGA











ATAC (902)
GTTT (903)











601
chr9:
chr9:
AATAGAACTTCC
AATAGAACTTCC
7
76
3.27
4.47E−08
3′ss
Mel.



101891382-
101891382-
AACTACTGGCCC
AACTACTGTAAA









101894778
101894790
TTTTTCAGTAAA
GTCATCACCTGG











GTCA (904)
CCTT (905)











588
chr11:
chr11:
CATGCCGGGGCC
CATGCCGGGGCC
0
11
3.58
1.83E−02
3′ss
Mel.



11988666-
11988645-
AGAGGATGGCTC
AGAGGATGCTCT









11989941
11989941
TTTCCACCTGTC
GCACCCGGGACA











TGCA (890)
GTGA (891)











589
chr16:
chr16:
GGCGAAGCAAGA
GGCGAAGCAAGA
0
11
3.58
1.88E−02
3′ss
Mel.



19838459-
19838459-
ACAAAAAGTATT
ACAAAAAGTGAA









19843229
19867808
TTCTTCTAGGAT
ATGCAAAATGGA











GGAA (892)
GGAC (893)











590
chr1:
chr1:
GGCTCCCATTCT
GGCTCCCATTCT
0
11
3.58
2.42E−03
3′ss
Mel.



155630724-
155630704-
GGTTAAAGAGTG
GGTTAAAGGCCA









155631097
155631097
TTCTCATTTCCA
GTCTGCCATCCA











ATAG (195)
TCCA (196)











591
chr1:
chr1:
GAAGAACAGGAT
GAAGAACAGGAT
0
11
3.58
1.74E−02
3′ss
Mel.



219366593-
219366593-
ATTAATAGTATG
ATTAATAGGAGG









219383856
219383873
TTTTTGTTTTTA
ATTCTCTATGGG











GGAG (894)
AGGA (895)











592
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
0
10
3.46
2.28E−04
3′ss
Mel.



5595521-
5595508-
AAGAGAGATTTT
AAGAGAGAAGCT









5598803
5598803
GGTAAACAGAGC
CCAAGAGTCAGG











TCCA (138)
ATCG (139)











593
chr5:
chr5:
CAATTCAGTAGA
AGGTCTTCCTGG
0
10
3.46
2.42E−02
5′ss
Mel.



462644-
462422-
TTCACCCTCAAC
ACCTGGAGCAAC









464404
464404
ATCTGAATGAAT
ATCTGAATGAAT











TGAT (896)
TGAT (897)











594
chr9:
chr9:
GGGAGATGGATA
GGGAGATGGATA
3
41
3.39
1.97E−10
3′ss
Mel.



35813153-
35813142-
CCGACTTGCTCA
CCGACTTGTGAT









35813262
35813262
ATTTCAGTGATC
CAACGATGGGAA











AACG (146)
GCTG (147)











595
chr1:
chr1:
AGAGGGCACGGG
AGAGGGCACGGG
2
29
3.32
1.42E−03
3′ss
Mel.



205240383-
205240383-
ACATCCAGCCCC
ACATCCAGGAGG









205240923
205240940
TCTGCCCCTGCA
CCGTGGAGTCCT











GGAG (898)
GCCT (899)











596
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
0
9
3.32
6.24E−03
3′ss
Mel.



125442465-
125442465-
TTGCCAGACCTT
TTGCCAGAGGAA









125445146
125445158
TTCTATAGGGAA
TCAAAGACTCCA











TCAA (150)
TCTG (151)











597
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
0
9
3.32
3.79E−04
3′ss
Mel.



71939542-
71939542-
TGCCTCAGTCAC
TGCCTCAGATGG









71939690
71939770
TTTACAGCTGCA
GGAGGATGAGAA











TCGT (47)
GCCC (48)











598
chr16:
chr16:
AGATGATTGAGG
AGATGATTGAGG
0
9
3.32
1.06E−02
3′ss
Mel.



70292147-
70292120-
CAGCCAAGCTCT
CAGCCAAGGCCG









70292882
70292882
TTTCTGTCTTCT
TCTATACCCAGG











TGGT (900)
ATTG (901)











599
chr2:
chr2:
GAGGAGCCACAC
GAGGAGCCACAC
0
9
3.32
2.20E−02
3′ss
Mel.



220044485-
220044485-
TCTGACAGATAC
TCTGACAGTGAG









220044888
220044831
CTGGCTGAGAGC
GGTGCGGGGTCA











TGGC (107)
GGCG (108)











600
chr3:
chr3:
GCTGCTCTCTTC
GCTGCTCTCTTC
0
9
3.32
2.87E−06
3′ss
Mel.



45043100-
45043100-
AATACAAGTGCT
AATACAAGGATA









45046767
45046782
TCTGCTTCCAGG
CCAAGGGTTCGA











ATAC (902)
GTTT (903)











601
chr9:
chr9:
AATAGAACTTCC
AATAGAACTTCC
7
76
3.27
4.47E−08
3′ss
Mel.



101891382-
101891382-
AACTACTGGCCC
AACTACTGTAAA









101894778
101894790
TTTTTCAGTAAA
GTCATCACCTGG











GTCA (904)
CCTT (905)











602
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
2
27
3.22
1.02E−05
3′ss
Mel.



7131030-
7131102-
CCCCCGAACCTA
CCCCCGAAATGA









7131295
7131295
TCCAGGTTCCTC
GCCCATCCAGCC











CTCC (33)
AATT (34)











603
chr17:
chr17:
TGTTACTGCAGT
TGTTACTGCAGT
1
17
3.17
2.33E−03
3′ss
Mel.



79556145-
79556145-
GGCTACAGGTCT
GGCTACAGGTGG









79563141
79563141
CTCTCTTGCAGG
TCCTGACAACCA











TGGT (906)
AGTC (907)











604
chr13:
chr13:
ACATCACAAAGC
ACATCACAAAGC
0
8
3.17
1.95E−03
3′ss
Mel.



45841511-
45841511-
AACCTGTGGGGT
AACCTGTGGTGT









45857556
45857576
TTTGTTTTTGTT
ACCTGAAGGAAA











TTAG (908)
TCTT (909)











605
chr14:
chr14:
GGTGCTGGCTGC
GGTGCTGGCTGC
0
8
3.17
3.94E−03
3′ss
Mel.



105176525-
105176525-
CTGCGAAACCCT
CTGCGAAAGCCT









105177255
105177273
GGCTGCCCCTGC
GCTCACCAGCCG











AGGC (910)
CCAG (911)











606
chr16:
chr16:
CACCAAGCAGAG
CACCAAGCAGAG
0
8
3.17
7.87E−04
3′ss
Mel.



15129410-
15129410-
GCTTCCAGTCTG
GCTTCCAGGCCA









15129852
15129872
TCTGCCCTTTCT
GAAGCCTTTTAA











GTAG (216)
AAGG (217)











607
chr17:
chr17:
CCTCTCTGCTCG
CCTCTCTGCTCG
0
8
3.17
7.21E−08
3′ss
Mel.



17062316-
17062316-
AGAAGGAGTGTG
AGAAGGAGCTGG









17064532
17064553
TGTCTTTTTGCC
AGCAGAGCCAGA











AACA (912)
AGGA (913)











608
chr19:
chr19:
ATCACAACCGGA
ATCACAACCGGA
0
8
3.17
1.45E−02
3′ss
Mel.



15491444-
15491423-
ACCGCAGGCTCC
ACCGCAGGCTCA









15507960
15507960
TTCTGCCCTGCC
TGATGGAGCAGT











CGCA (661)
CCAA (662)











609
chr3:
chr3:
CTGGAAGCTCAA
CTGGAAGCTCAA
0
8
3.17
4.68E−04
3′ss
Mel.



112724877-
112724851-
GGTACTAGATTT
GGTACTAGTTTG









112727017
112727017
TTCCTCTCTCTG
CCAAAGAAACTA











TCTT (914)
GAGT (915)











610
chr1:
chr1:
CCCGAGCTCAGA
CCCGAGCTCAGA
4
41
3.07
3.31E−04
3′ss
Mel.



3548881-
3548902-
GAGTAAATTCTC
GAGTAAATATGA









3549961
3549961
CTTACAGACACT
GATCGCCTCTGT











GAAA (177)
CCCA (178)











611
chr2:
chr2:
TATCCATTCCTG
TATCCATTCCTG
1
15
3.00
3.44E−05
3′ss
Mel.



178096758-
178096736-
AGTTACAGTATA
AGTTACAGTGTC









178097119
178097119
AACTTCCTTCTC
TTAATATTGAAA











ATGC (156)
ATGA (157)











612
chr11:
chr11:
CGGCGATGACTC
CGGCGATGACTC
0
7
3.00
2.48E−02
3′ss
Mel.



62554999-
62554999-
GGACCCAGCTTC
GGACCCAGGGCT









62556481
62556494
TCTCCACAGGGC
CCTTCAGTGGTA











TCCT (916)
GATG (917)











613
chr15:
chr15:
CCGCCAGGAGAA
CCGCCAGGAGAA
0
7
3.00
9.38E−04
3′ss
Mel.



41102168-
41102168-
CAAGCCCATCCC
CAAGCCCAAGTT









41102274
41102268
CTCACAGGCAGA
AGTCCCCTCACA











GATA (918)
GGCA (919)











614
chr16:
chr16:
CAGCAGCAGCTC
CAGCAGCAGCTC
0
7
3.00
9.09E−03
3′ss
Mel.



48311390-
48311390-
TGCTTGAGCTAC
TGCTTGAGGTGT









48330007
48329925
TGCCAACACCAC
TGGATCCTGAAC











TGCT (920)
AAAA (921)











615
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
7
3.00
6.35E−04
3′ss
Mel.



26437445-
26437430-
GGTGGAAACATT
GGTGGAAAAATT









26437921
26437921
TTATTTTACAGA
GACAGCGTATGC











ATTG (295)
CATG (296)











616
chr3:
chr3:
GCACTTATGGTG
GCACTTATGGTG
0
7
3.00
1.74E−07
3′ss
Mel.



48638222-
48638273-
GTGGCGTGAGTT
GTGGCGTGCACC









48638407
48638407
TCCAGACCTTCA
TGTCCAGCCCAC











GCAT(922)
TGGC (923)











617
chr19:
chr19:
GTGCTTGGAGCC
GTGCTTGGAGCC
4
35
2.85
1.91E−07
3′ss
Mel.



55776746-
55776757-
CTGTGCAGACTT
CTGTGCAGCCTG









55777253
55777253
TCCGCAGGGTGT
GTGACAGACTTT











GCGC (179)
CCGC (180)











618
chr9:
chr9:
GTGGCTCCAGTA
GACCTGCTCAAG
8
63
2.83
2.74E−02
5′ss
Mel.



119414072-
119414072-
TCAGAAAGAGAC
TTCACTCAAGAC









119488049
II9449344
CACAGAGCTGGG
CACAGAGCTGGG











CAGC (924)
CAGC (925)











619
chr10:
chr10:
TGTGGGCATGGA
TGTGGGCATGGA
0
6
2.81
8.27E−08
3′ss
Mel.



82264534-
82264534-
GCGAAAAGTGCT
GCGAAAAGGGTG









82266954
82266983
GCCCTGCTTTCT
TGCTGTCCGACC











CTGT (926)
TCAC (927)











620
chr12:
chr12:
TTCCTCTTCCCC
TTCCTCTTCCCC
0
6
2.81
4.32E−06
3′ss
Mel.



56361953-
56361953-
TCATCAAGTCCT
TCATCAAGAGCT









56362539
56362561
CTCTTTCTCCTT
ATCTGTTCCAGC











TGTC (928)
TGCT (929)











621
chr19:
chr19:
GGGGCACTGACA
GGGGCACTGACA
0
6
2.81
2.67E−02
3′ss
Mel.



50149459-
50149459-
CGGCTACTAGCC
CGGCTACTGTGT









50149761
50149782
TCTCTGGCCTCT
TGGACATGGCCA











TCCA (930)
CGGA (931)











622
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
6
2.81
1.25E−04
3′ss
Mel.



34144042-
34144042-
ACGGAGAGTTCT
ACGGAGAGGTAC









34144761
34144743
CTGTGACCAGAC
TGAGGACAAATC











ATGA (250)
AGTT (50)











623
chrX:
chrX:
TGACTCCGCTGC
TGACTCCGCTGC
0
6
2.81
1.80E−02
3′ss
Mel.



118923962-
118923974-
TCGCCATGACTT
TCGCCATGTCTT









118925536
118925536
TCAGGATTAAGC
CTCACAAGACTT











GATT (697)
TCAG (698)











624
chr2:
chr2:
CCCCTGAGATGA
CCCCTGAGATGA
3
25
2.70
6.46E−06
exon
Mel.



27260570-
27260570-
AGAAAGAGCTCC
AGAAAGAGCTCC




incl.




27260682
27261013
CTGTTGACAGCT
TGAGCAGCCTGA











GCCT (183)
CTGA (184)











625
chr2:
chr2:
AGGCTGTAGCAG
AGGCTGTAGCAG
1
12
2.70
2.24E−02
3′ss
Mel.



99225189-
99225189-
GACTCCAGGGTT
GACTCCAGGAAG









99226105
99226218
GGGAAGAACATG
ATGTTACCGAGT











GAAA (932)
ACTT (933)











626
chr8:
chr8:
CCGAGGATGCTA
CCGAGGATGCTA
4
30
2.63
6.42E−03
3′ss
Mel.



133811106-
133811106-
AGGGGCAGTTTC
AGGGGCAGGATT









133811328
133816063
TGTTCCAGGTGA
GGATAGCTTTAG











AATC (934)
TCAA (935)











627
chr21:
chr21:
GCCTCCCGGTCC
GCCTCCCGGTCC
4
29
2.58
9.60E−04
3′ss
Mel.



46935066-
46936054-
GCAAGCAGAATG
GCAAGCAGTTCC









46945730
46945730
AAGAACTGCATG
AGTTATACTCCG











TGGC (936)
TGTA (937)











628
chr17:
chr17:
TCGTAACAGGGG
CTGTGACGGGTG
3
23
2.58
1.22E−02
exon
Mel.



27210249-
27210249-
TTGCACAGGTGA
TCGCCCAGGTGA




skip




27212874
27211242
AGATCATGACGG
AGATCATGACGG











AGAA (938)
AGAA (939)











629
chr6:
chr6:
GTTTGGGGAAGT
GTTTGGGGAAGT
1
11
2.58
2.07E−05
exon
Mel.



112020873-
112017659-
ATGGATGGAGAA
ATGGATGGGTAC




incl.




112021306
112021306
AGCTGATGGTTT
CTGGAATGGAAA











GTGT (940)
CACA (941)











630
chr6:
chr6:
TAACTAATCCTT
CAGCCTACCAGA
1
11
2.58
4.06E−02
5′ss
Mel.



39854223-
39851845-
CTCAGCAGAAAG
GGCACCAGAAAG









39855261
39855261
AGCTGGGCTCCA
AGCTGGGCTCCA











CTGA (942)
CTGA (943)











631
chr11:
chr11:
AGTCCAGCCCCA
AGTCCAGCCCCA
0
5
2.58
9.35E−03
3′ss
Mel.



64900740-
64900723-
GCATGGCACCTC
GCATGGCAGTCC









64900940
64900940
TCCCCACTCCTA
TGTACATCCAGG











GGTC (136)
CCTT (137)











632
chr16:
chr16:
GGATCCTTCACC
GGATCCTTCACC
0
5
2.58
1.87E−03
3′ss
Mel.



1402307-
1402307-
CGTGTCTGTCTT
CGTGTCTGGACC









1411686
1411743
TGCAGACAGGTT
CGTGCATCTCTT











CTGT (85)
CCGA (86)








633
chr17:
chr17:
GCATCTCAGCCC
GCATCTCAGCCC
0
5
2.58
1.16E−05
3′ss
Mel.



16344444-
16344444-
AAGAGAAGTTTC
AAGAGAAGGTTA









16344670
16344681
TTTGCAGGTTAT
TATTCCCAGAGG











ATTC (287)
ATGT (288)











634
chr1:
chr1:
CTACACAGAGCT
CTACACAGAGCT
0
5
2.58
2.48E−06
3′ss
Mel.



32096333-
32096443-
GCAGCAAGGTGT
GCAGCAAGCTCT









32098095
32098095
GCACCCAGCTGC
GTCCCAAATGGG











AGGT (291)
CTAC (292)











635
chr22:
chr22:
CCTGCGCAACTG
CCTGCGCAACTG
0
5
2.58
1.56E−04
3′ss
Mel.



19164146-
19164206-
GTACCGAGGCGC
GTACCGAGGGGA









19164358
19164358
AGCCAGTGTCTT
CAACCCCAACAA











TGGA (944)
GCCC (945)











636
chr3:
chr3:
ATAAAAATTGCT
ATAAAAATTGCT
0
5
2.58
2.28E−03
3′ss
Mel.



131181737-
131181719-
TAGTAAAGATTT
TAGTAAAGGTCA









131186934
131186934
TTGCCTTCTCTC
AAGATTCTAAAC











AGGT (946)
TGCC (947)











637
chrX
chr8:
TGAGTTCATGGA
TGAGTTCATGGA
0
5
2.58
3.48E−02
3′ss
Mel.



98817692-
98817692-
TGATGCCAAAAT
TGATGCCAACAT









98827531
98827555
TCTTTTTAATCT
GTGCATTGCCAT











TTCG (948)
TGCG (949)











638
chrX:
chrX:
AGAGTTGAAAAA
AGAGTTGAAAAA
0
5
2.58
4.97E−03
3′ss
Mel.



24091380-
24091380-
CACTGGCGTCTC
CACTGGCGTTTA









24092454
24094838
CTTTTCAGGAAT
ATTGGTTGGGGT











CACA (950)
CAGA (951)











639
chr12:
chr12:
GGCCAGCCCCCT
GGCCAGCCCCCT
8
51
2.53
3.07E−09
3′ss
Mel.



120934019-
120934019-
TCTCCACGGCCT
TCTCCACGGTAA









120934204
120934218
TGCCCACTAGGT
CCATGTGCGACC











AACC (206)
GAAA (207)











640
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
3
21
2.46
2.87E−02
3′ss
Mel.



125023777-
125023787-
GCCACGAGACAT
GCCACGAGTATT









125026993
125026993
TGATGGAAGCAG
TCATAGACATTG











AAAC (142)
ATGG (143)











641
chr1O:
chr1O:
TGGGGCCACAAA
TGGGGCCACAAA
4
24
2.32
1.77E−02
exon
Mel.



74994698-
74994698-
GACAGATGCTGG
GACAGATGAAAC




skip




74999069
74994950
ATACACAGTATC
CCCATGGCGACT











GTCG (952)
CTAG (953)











642
chr1:
chr1:
CTTGCCTTCCCA
CTTGCCTTCCCA
1
9
2.32
1.49E−04
3′ss
Mel.



154246074-
154246074-
TCCTCCTGCAAA
TCCTCCTGAACT









154246225
154246249
CACCTGCCACCT
TCCAGGTCCTGA











TTCT (289)
GTCA (290)











643
chr11:
chr11:
GGGGACAGTGAA
GGGGACAGTGAA
0
4
2.32
1.19E−05
3′ss
Mel.



57100545-
57100623-
ATTTGGTGGCAA
ATTTGGTGGGCA









57100908
57100908
GAATGAGGTGAC
GCTGCTTTCCTT











ACTG (103)
TGAC (104)











644
chr16:
chr16:
GAACTGGCACCG
GAACTGGCACCG
0
4
2.32
1.03E−03
3′ss
Mel.



313774-
313774-
ACAGACAGTGTC
ACAGACAGATCC









313996
314014
CCCTCCCTCCCC
TGTTTCTGGACC











AGAT (244)
TTGG (245)











645
chr17:
chr17:
AACATGGAATCA
AACATGGAATCA
0
4
2.32
1.03E−03
3′ss
Mel.



34147441-
34147441-
TCAGGAAGTTCT
TCAGGAAGCCAA









34149625
34149643
CCATTTCTATTT
GGTGGAAGAGCA











AGCC (954)
CCTT (955)











646
chr1:
chr1:
CGTGCGTGTGTG
CTTAGGAAAGAC
0
4
2.32
2.87E−02
5′ss
Mel.



1480382-
1480382-
TGCTCTTGCTAT
AAAGAACTCTAT









1497319
1500152
ACACAGAATGGG
ACACAGAATGGG











ATTT (956)
ATTT (957)











647
chr22:
chr22:
CCCAGCCTGCTG
CCCAGCCTGCTG
0
4
2.32
3.33E−02
3′ss
Mel.



24108483-
24108462-
TCCAGCAGCCTC
TCCAGCAGGCCC









24109560
24109560
TTGCACTGTACC
CCACCCCCGCTG











CCCA (958)
CCCC (959)











648
chr22:
chr22:
ACCCAAGGCTCG
ACCCAAGGCTCG
0
4
2.32
5.75E−03
3′ss
Mel.



44559810-
44559810-
TCCTGAAGTTTC
TCCTGAAGACGT









44564460
44564481
TCTGTTTCCTTC
GGTTAACTTGGA











TGCA (960)
CCTC (961)











649
chr5:
chr5:
AGATTGAAGCTA
AGATTGAAGCTA
0
4
2.32
1.38E−03
3′ss
Mel.



132439718-
132439718-
AAATTAAGTTTT
AAATTAAGGAGC









132439902
132439924
CTGTCTTACCCA
TGACAAGTACTT











TTCC (348)
GTAG (349)











650
chr5:
chr5:
GAACCCGGTGGT
GAACCCGGTGGT
0
4
2.32
5.33E−04
3′ss
Mel.



175815974-
175815974-
ACCCATAGTTGC
ACCCATAGGTTG









175816311
175816331
TTTGTCCCCTCC
CCTGGCCACGGC











TCAG (962)
GGCC (963)











651
ch17:
chr7:
AATGGAAGTACC
AATGGAAGTACC
0
4
2.32
7.50E−03
3′ss
Mel.



74131270-
74131270-
AGCAGAAGAATT
AGCAGAAGATTC









74133179
74133197
TTATTTTTTTCA
TACTCAACATGT











AGAT (964)
CCCT (965)











652
chr20:
chr20:
GGCAGCTGTTAG
GGCAGCTGTTAG
7
37
2.25
4.91E−02
exon
Mel.



57227143-
57227143-
CCGAGCAAGAGC
CCGAGCAACTTG




incl.




57234678
57242545
TGGACGAGGTAT
CTGATGACCGTA











TGTG (966)
TGGC (967)











653
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
3
18
2.25
1.03E−03
3′ss
Mel.



54954250-
54954322-
ATAAGGAGTTCT
ATAAGGAGGTAA









54957496
54957496
CTTGTAGGATGC
AACCTGTTTAGA











CACT (313)
AATT (314)











654
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
14
70
2.24
5.98E−06
3′ss
Mel.



129771378-
129771384-
GGAATCAGTATC
GGAATCAGCCTT









129790554
129790554
ACAGGCAGAAGC
AGTATCACAGGC











TCTG (303)
AGAA (304)











655
chr13:
chr13:
GTTTAGAAATGG
GTTTAGAAATGG
18
88
2.23
1.12E−04
3′ss
Mel.



45911538-
45911523-
AAAAATGTTTTT
AAAAATGTTAAC









45912794
45912794
TGCTTTTACAGT
AAATGTGGCAAT











AACA (968)
TATT (969)











656
chr2:
chr2:
CCAAGAGACAGC
CCCCTGAGATGA
5
27
2.22
4.64E−05
exon
Mel.



27260760-
27260570-
ACATTCAGCTCC
AGAAAGAGCTCC




incl.




27261013
27261013
TGAGCAGCCTGA
TGAGCAGCCTGA











CTGA (315)
CTGA (184)











657
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
8
2.17
6.85E−03
3′ss
Mel.



23398690-
23398690-
CCCCCAAGTCCT
CCCCCAAGTGAT









23399766
23399784
TTGTTCTTTTGC
GTATATCTCTCA











AGTG (210)
TCAA (211)











658
chr6:
chr6:
AGGATGTGGCTG
AGGATGTGGCTG
1
8
2.17
2.70E−05
3′ss
Mel.



31602334-
31602334-
GCACAGAAGTGT
GCACAGAAATGA









31602574
31602529
CATCAGGTCCCT
GTCAGTCTGACA











GCAG (148)
GTGG (149)











659
chr3:
chr3:
AAATCTCGTGGA
AAATCTCGTGGA
7
33
2.09
4.05E−02
3′ss
Mel.



16310782-
16310782-
CTTCTAAGTTTT
CTTCTAAGAAAG









16312435
16312451
CTGTTTGCCCAG
CGCCATGGCCTG











AAAG (970)
TGCT (971)











660
chr11:
chr11:
AGTTCCGGGGCT
AGTTCCGGGGCT
0
3
2.00
2.75E−02
3′ss
Mel.



68838888-
68838888-
ACCTGATGCCTT
ACCTGATGAAAT









68839375
68839390
CCTCTTTGCAGA
CTCTCCAGACCT











AATC (972)
CGCT (973)











661
chr12:
chr12:
GGCACCCCAAAA
GGCACCCCAAAA
0
3
2.00
1.12E−02
3′ss
Mel.



58109976-
58109976-
GATGGCAGATCA
GATGGCAGGTGC









58110164
58110194
GTCTCTCCCTGT
GAGCCCGACCAA











TCTC (285)
GGAT (286)











662
chr1:
chr1:
AAGAAGGAATCC
AAGAAGGAATCC
0
3
2.00
7.34E−03
3′ss
Mel.



32377442-
32377427-
ACGTTCTAGTCA
ACGTTCTAGATT









32381495
32381495
TTTCTTTTCAGG
GGCCATTTGATG











ATTG (974)
ATGG (975)











663
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
3
2.00
2.55E−02
3′ss
Mel.



36627471-
36627512-
GAACCCAGGACC
GAACCCAGAGAG









36629198
36629198
AAGTGAGCAGAG
CAGTATCTTTAT











AGAA (976)
TGAG (200)











664
chr3:
chr3:
GCAACCAGTTTG
GCAACCAGTTTG
0
3
2.00
3.20E−03
3′ss
Mel.



49395199-
49395180-
GGCATCAGCTGC
GGCATCAGGAGA









49395459
49395459
CCTTCTCTCCTG
ACGCCAAGAACG











TAGG (342)
AAGA (343)











665
chr6:
chr6:
AGCCCCTGCTTG
AGCCCCTGCTTG
0
3
2.00
4.68E−04
3′ss
Mel.



170844509-
170844493-
ACAACCAGTTTC
ACAACCAGGTTG









170846321
170846321
ATGTCCCACCAG
GTTTTAAGAACA











GTTG (977)
TGCA (978)











666
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
0
3
2.00
4.46E−02
3′ss
Mel.



139837449-
139837395-
CTGTGAAGGCCC
CTGTGAAGATCT









139837800
139837800
CCGCCCCGCGAC
GGAGCAACGACC











CTGG (175)
TGAC (176)











667
chr10:
chr10:
TTGGCTGTAGGA
TTGGCTGTAGGA
8
34
1.96
2.70E−05
exon
Mel.



103904064-
103904064-
AACTCAGGGTCC
AACTCAGGCGGC




skip




103908128
103904776
AGCTGTAGTTCC
GTTGACATTCCC











TCTG (979)
CAGG (980)











668
chr17:
chr17:
TGTATCTCCGAC
TGTATCTCCGAC
6
26
1.95
3.79E−02
exon
Mel.



27212965-
27211333-
ACTCAGAGACTG
ACTCAGAGGATT




incl.




27215962
27215962
TCTCTGGAGGTT
TCCCTAGAGATT











ATGA (981)
ATGA (982)











669
chrX:
chrX:
AGGCTGATCTAC
AGGCTGATCTAC
2
10
1.87
5.30E−03
3′ss
Mel.



15849691-
15845495-
TGCAGGAGCCAC
TGCAGGAGGAAG









15863501
15863501
GTCATGAATATT
CTGAAACCCCAC











TTAA (983)
GTAG (984)











670
chr2:
chr2:
GGAAATGGGACA
GGAAATGGGACA
14
52
1.82
4.43E−06
3′ss
Mel.



230657846-
230657861-
GGAGGCAGAGGA
GGAGGCAGCTTT









230659894
230659894
TCACAGGCTTTA
TCTCTCAACAGA











AAAT (387)
GGAT (388)











671
chr5:
chr5:
GCTCAGCCCCCT
TGACCCTGCAGC
5
20
1.81
2.74E−03
exon
Mel.



141694720-
141694720-
CCCCACAGGGCC
TCCTCAAAGGCC




incl.




141699308
141704408
CCTAGAAGCCTG
CCTAGAAGCCTG











TTTC (985)
TTTC (986)











672
chr19:
chr19:
GCCGACCCGCCT
GCCGACCCGCCT
3
13
1.81
4.16E−03
3′ss
Mel.



3542975-
3544730-
GCGACGCTCTTT
GCGACGCTGGGA









3544806
3544806
TCTTGCCTGGAG
CCGTGATGCCCG











AAGA (987)
GCCC (988)











673
chr3:
chr3:
TGCGGAGACCCC
TGCGGAGACCCC
1
6
1.81
2.67E−02
exon
Mel.



58417711-
58419411-
TTCGGGAGGTGA
TTCGGGAGGTCT




skip




58419494
58419494
CAGTTCGTGATG
CCGGGCTGCTGA











CTAT (989)
AGAG (990)











674
chr6:
chr6:
CTATCAGTAGGT
GCATTGATGTGG
1
6
1.81
2.71E−03
exon
Mel.



108370622-
108370622-
TTTTAGAGATGA
AAGATGCAATGA




incl.




108370735
108372234
ACATCACTCGAA
ACATCACTCGAA











AACT (991)
AACT (992)











675
chr6:
chr6:
GCATTGATGTGG
GCATTGATGTGG
1
6
1.81
1.84E−03
exon
Mel.



108370787-
108370622-
AAGATGCAGTTT
AAGATGCAATGA




incl.




108372234
108372234
TTTTCCTGGCAG
ACATCACTCGAA











AAGA (993)
AACT (992)











676
chr6:
chr6:
CAGTGGGCGGAT
CAGTGGGCGGAT
1
6
1.81
1.04E−02
3′ss
Mel.



166779550-
166779594-
GACATTTGGTAC
GACATTTGCCCT









166780282
166780282
AGCCTCGGAACT
CTGTTGCTATTC











GGCT (994)
TTTG (995)











677
chr7:
chr7:
GGTGTCCATGGC
GGTGTCCATGGC
1
6
1.81
4.73E−02
exon
Mel.



128033792-
128033082-
CTGCACTCCTAT
CTGCACTCTTAC




incl.




128034331
128034331
ACCTTTCTGCCG
GAAAAGCGGCTG











TGTA (996)
TACT (997)











678
chr6:
chr6:
ACTGGGAAGTTC
ACTGGGAAGTTC
10
37
1.79
1.30E−02
exon
Mel.



136597127-
136597646-
TTAAAAAGTCCC
TTAAAAAGGTTC




skip




136599002
136599002
CCTCTACACAAG
ACAGATGAAGAG











AATC (998)
TCTA (999)











679
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
20
69
1.74
1.28E−05
3′ss
Mel.



54954239-
54954322-
ATAAGGAGGATG
ATAAGGAGGTAA









54957496
54957496
CCACTGGAAATG
AACCTGTTTAGA











TTGA (322)
AATT (314)











680
chr4:
chr4:
GCTGAGCGGGGC
TCCAACAAGCAC
20
69
1.74
4.13E−05
exon
Mel.



17806394-
17806394-
GACCCGAGTCTT
CTCTGAAGTCTT




skip




17812069
17806729
CTCATTCACAGG
CTCATTCACAGG











TTAA (1000)
TTAA (832)











681
chr19:
chr19:
AGTGGCAGTGGC
AGTGGCAGTGGC
8
29
1.74
8.03E−04
3′ss
Mel.



6731065-
6731122-
TGTACCAGCCCA
TGTACCAGCTCT









6731209
6731209
CAGGAAACAACC
TGGTGGAGGGCT











CGTA (311)
CCAC (312)











682
chr16:
chr16:
TGTTCCACCTCC
TGTTCCACCTCC
6
22
1.72
2.96E−02
3′ss
Mel.



28842393-
28842393-
TCCTGCAGCTCC
TCCTGCAGTGGG









28843507
28843525
CCCTTTTCTTCC
CCGGATGTATCC











AGTG (1001)
CCCG (1002)











683
chr3:
chr3:
ACCCATGAGAAT
CTGGCCCCTGAG
8
28
1.69
8.95E−03
exon
Mel.



50615004-
50616357-
GCTCAGAGCTAT
ATCCGCAGCTAT




skip




50617274
50617274
GAAGACCCCGCG
GAAGACCCCGCG











GCCC (1003)
GCCC (1004)











684
chr11:
chr11:
CAAGCTCGAGTC
CAAGCTCGAGTC
4
15
1.68
8.31E−03
exon
Mel.



772521-
773629-
CATCGATGAACC
CATCGATGGTGC




skip




774007
774 (X)7
CATCTGCGCCGT
CCGGTACCATGC











CGGC (1005)
CCTC (1006)











685
chr2:
chr2:
CTTCACTGTCAC
CTTCACTGTCAC
9
30
1.63
2.25E−02
3′ss
Mel.



220424219-
220426730-
CGTCACAGAACC
CGTCACAGAGTC









220427123
220427123
CCCAGTGCGGAT
TTACCAAAGTCA











CATA (1007)
GGAC (1008)











686
chr3:
chr3:
GTCTTCCAATGG
GTCTTCCAATGG
10
33
1.63
1.04E−02
3′ss
Mel.



148759467-
148759455-
CCCCTCAGCCTT
CCCCTCAGGAAA









148759952
148759952
TTCTCTAGGAAA
TGATACACCTGA











TGAT (234)
AGAA (235)











687
chr5:
chr5:
AGAAACAGAAAC
AGAAACAGAAAC
5
17
1.58
1.55E−02
exon
Mel.



34945908-
34945908-
CAGCACAGGATG
CAGCACAGAATT




incl.




34949647
34950274
TACCTGGCAAAG
ATGATGACAATT











ATTC (1009)
TCAA (1010)











688
ch16:
chr6:
TTCTGCATCTGT
AAAGGAGTGCTT
2
8
1.58
1.45E−02
exon
Mel.



158589427-
158591570-
GGGCCGAGTGAT
ATAGAATGTGAT




skip




158613008
158613008
CCTGCCATGAAG
CCTGCCATGAAG











CAGT (1011)
CAGT (1012)











689
chr14:
chr14:
AGGATCGGCAAC
CTGGGATAAGAG
1
5
1.58
1.98E−02
exon
Mel.



23495584-
23495584-
ATGGCAAGGCCT
AGGCCCTGGCCT




incl.




23496953
23502576
CTACTACGTGGA
CTACTACGTGGA











CAGT (1013)
CAGT (1014)











690
chr6:
chr6:
GTTCAGGACACA
GGGAGGGAGAGA
1
5
1.58
1.23E−02
exon
Mel.



33669197-
33669197-
ATAAGCAGGTTG
ATACCCAGGTTG




incl.




33678471
33679325
CAGAGCCTGAGG
CAGAGCCTGAGG











CCTG (1015)
CCTG (1016)











691
chr10:
chr10:
TACCCGGATGAT
TACCCGGATGAT
0
2
1.58
2.58E−04
3′ss
Mel.



102286851-
102286831-
GGCATGGGAAGT
GGCATGGGGTAT









102289136
102289136
TCTTGCTGTCTT
GGCGACTACCCG











TCAG (1017)
AAGC (1018)











692
chr11:
chr11:
GACATATGAGTC
GACATATGAGTC
0
2
1.58
2.45E−02
3′ss
Mel.



66333872-
66333875-
AAAGGAAGCCCG
AAAGGAAGAAGC









66334716
66334716
GTGGCGCCTGTC
CCGGTGGCGCCT











CGTC (1019)
GTCC (1020)











693
chr11:
chr11:
CGGATCAACTTC
CGGATCAACTTC
0
2
1.58
2.65E−03
3′ss
Mel.



8705628-
8705628-
GACAAATAGTGG
GACAAATACCAC









8706243
8706264
TTGTTACCTCTT
CCAGGCTACTTT











CCTA (1021)
GGGA (1022)











694
chr12:
chr12:
TTATAGGCGTGA
TTATAGGCGTGA
0
2
1.58
1.03E−03
3′ss
Mel.



53421972-
53421972-
TGATAGAGTTTC
TGATAGAGGTCC









53427574
53427589
ATTTAACTTAGG
CCCCCAAAGACC











TCCC (1023)
CAAA (1024)











695
chr15:
chr15:
TGGAAATATTTC
GCCTCACTGAGC
0
2
1.58
7.87E−03
exon
Mel.



25212387-
25207356-
TAGACTTGGTGT
AACCAAGAGTGT




incl.




25213078
25213078
CAGTTGTACCCG
CAGTTGTACCCG











AGGC (1025)
AGGC (145)











696
chr1:
chr1:
TCGGCCCAGAAG
CTTAGGAAAGAC
0
2
1.58
4.66E−02
5′ss
Mel.



1480382-
1480382-
AACCCCGCCTAT
AAAGAACTCTAT









1497338
1500152
ACACAGAATGGG
ACACAGAATGGG











ATTT (1026)
ATTT (957)











697
chr5:
chr5:
TCTATATCCCCT
TCTATATCCCCT
0
2
1.58
1.26E−04
3′ss
Mel.



177576859-
177576839-
CTAAGACGCACT
CTAAGACGGACC









177577888
177577888
TCTTTCCCCTCT
TGGGTGCAGCCG











GTAG (299)
CAGG (300)











698
chr6:
chr6:
GCTGAAGGGAAA
GCTGAAGGGAAA
0
2
1.58
4.68E−02
3′ss
Mel.



42905945-
42905945-
AGACACCAAAAC
AGACACCAGTTG









42911535
42906305
ACAAACAGCAGA
CCTGGCAGAGCA











ATGG (1027)
GTGG (1028)











699
chr17:
chr17:
CATCATCAAGTT
CATCATCAAGTT
5
16
1.5
1.74E−04
intron
Mel.



2282497-
2282497-
TTTCAATGACGA
TTTCAATGAACG




reten-




2282499
2282725
GCTGGTCCAGCC
TGCTGAGCATCA




tion






ATCC (1029)
CGAT (1030)











700
chr8:
chr8:
GAGGGCCTGCTC
ACATGCTTCAAA
23
66
1.48
1.49E−03
exon
Mel.



74601048-
74601048-
ATTCAAAGATGT
TAAATCAGATGT




incl.




74621266
74650518
TCTCAGTGCAGC
TCTCAGTGCAGC











TGAG (1031)
TGAG (1032)











701
chr10:
chr10:
CTGAGGCTAATG
CTGAGGCTAATG
14
40
1.45
2.13E−02
3′ss
Mel.



35495979-
35495979-
AAAAACAGGGAA
AAAAACAGGGAA









35500583
35500181
GCTGCCAAAGAA
GCTGCCCGGGAG











TGTC (1033)
TGTC (1034)











702
chr3:
chr3:
CGGCTGGGACTC
CGGCTGGGACTC
12
34
1.43
1.81E−02
3′ss
Mel.



119180951-
119180995-
TTCCATGCGTGG
TTCCATGCAGTT









119182182
119182182
CACTGGAAGCAG
GAAACTGGTTGA











ACTG (1035)
CAAC (1036)











703
chr4:
chr4:
AGTGAATGTAGT
AGTGAATGTAGT
17
47
1.42
2.45E−02
exon
Mel.



169919436-
169911479-
TGCACCAGTGAC
TGCACCAGGATT




incl.




169923221
169923221
AATACTTGTATG
TGTACACACAGA











GAGT (1037)
TATG (1038)











704
chr17:
chr17:
ATTCACACAGAG
TGAGGATCAATC
2
7
1.42
1.30E−02
exon
Mel.



55074416-
55075859-
CCACCTAGGCCA
CTGGGGAGGCCA




skip




55078215
55078215
GGCTACCAACGT
GGCTACCAACGT











CTTT (1039)
CTTT (1040)











705
chrX:
chrX:
AGAAACCTTGAA
AGAAACCTTGAA
7
20
1.39
3.40E−02
exon
Mel.



2310515-
2209644-
CGACAAAGAGAC
CGACAAAGTGGA




incl.




2326785
2326785
GTGAGTCTTGCT
ATTTTTATACTG











GTGT (496)
TGAC (495)











706
chrY:
chrY:
AGAAACCTTGAA
AGAAACCTTGAA
7
20
1.39
3.40E−02
exon
Mel.



2260515-
2159644-
CGACAAAGAGAC
CGACAAAGTGGA




incl.




2276785
2276785
GTGAGTCTTGCT
ATTTTTATACTG











GTGT (496)
TGAC (495)











707
chr5:
chr5:
TGGAAAAGTATA
TGGAAAAGTATA
4
12
1.38
2.71E−02
exon
Mel.



54456224-
54456224-
AAGGCAAAATTC
AAGGCAAAGTTT




skip




54459882
54456821
TTCAAAGAAGGA
CACTAGTTGTAA











ACCA (1041)
ACGT (1042)











708
chr15:
chr15:
ATACTAAGAACA
ATACTAAGAACA
19
50
1.35
2.54E−02
exon
Mel.



76146828-
76146828-
ACAATTTGAATG
ACAATTTGCTTC




skip




76161291
76152218
GGACAACAGAAG
GTCAGCAATTGA











AAGT (1043)
AGTG (1044)











709
chr8:
chr8:
TGGCCTTGACCT
TGGCCTTGACCT
7
19
1.32
3.77E−02
3′ss
Mel.



38270113-
38271322-
CCAACCAGGTCC
CCAACCAGGAGT









38271435
38271435
TGCACCCAGACC
ACCTGGACCTGT











TCAC (1045)
CCAT (1046)











710
chr1:
chr1:
GAAGGCAGCTGA
GAAGGCAGCTGA
3
9
1.32
1.42E−02
3′ss
Mel.



11131045-
11131030-
GCAAACAGTTCT
GCAAACAGCTGC









11132143
11132143
CTCCCTTGCAGC
CCGGGAACAGGC











TGCC (393)
AAAG (394)











711
chr11:
chr11:
TCCTTGAACACT
TCCTTGAACACT
1
4
1.32
2.52E−02
exon
Mel.



62556898-
62556898-
ACAATTAGACCT
ACAATTAGCTGT




skip




62557357
62557072
cttcttgggtga
TCTGAAGCCCAG











ATTT (1047)
AAAA (1048)




exon






712
chr14:
chr14:
ACACCATTGAGG
ACACCATTGAGG
1
4
1.32
1.92E−02
skip
Mel.



69349309-
69349772-
AGATCCAGGTGC
AGATCCAGGGAC









69350884
69350884
GGCAGCTGGTGC
TGACCACAGCCC











CTCG (1049)
ATGA (1050)











713
chr1:
chr1:
CCCATGTATAAG
CCCATGTATAAG
1
4
1.32
2.77E−02
3′ss
Mel.



155227125-
155227177-
GCTTTCCGGATG
GCTTTCCGGAGT









155227288
155227288
TGCTCTTTGTCC
GACAGTTCATTC











TCCA (1051)
AATT (1052)











714
chr20:
chr20:
CTCCCAGTGCTG
GAGCTGCCACGG
1
4
1.32
2.02E−02
exon
Mel.



25281520-
25281520-
TATATCCCGGAA
ATACTGAGGGAA




incl.




25281967
25282854
TTCCTGGGGAAG
TTCCTGGGGAAG











TCGG (1053)
TCGG (1054)











715
Chr7:
chr7:
GGATGCGCGTCT
AGCCGCAGAGCA
1
4
1.32
4.91E−02
exon
Mel.



142962185-
142962389-
GGTCAAGGGCTG
TCCTGGCGGCTG




skip




142964709
142964709
CAGAGAAGGCTG
CAGAGAAGGCTG











GTAT (1055)
GTAT (1056)











716
chr8:
chr8:
ACATGCTTCAAA
ACATGCTTCAAA
24
61
1.31
1.74E−02
exon
Mel.



74621397-
74601048-
TAAATCAGCTTC
TAAATCAGATGT




incl.




74650518
74650518
TCTCCAAGATAA
TCTCAGTGCAGC











AATG (1057)
TGAG (1032)











717
chr15:
chr15:
AACAAAGAAATA
CTGAGTCTTTAT
16
41
1.3
1.66E−03
exon
Mel.



49309825-
49309825-
ATTCACAGGATG
ATTTTGAGGATG




skip




49319561
49311614
AAGATGGGTTTC
AAGATGGGTTTC











AAGA (1058)
AAGA (1059)











718
chrX:
chrX:
TAGCCACCACTG
GGGAAAAGTCTT
11
28
1.27
1.07E−02
exon
Mel.



148582568-
148582568-
TGTGCCAGGGAT
TCACCCTGGGAT




incl.




148583604
148584841
ATCTTCTAACCA
ATCTTCTAACCA











TACC (1060)
TACC (1061)











719
chr12:
chr12:
CCTACCAGCCAC
CCTACCAGCCAC
4
11
1.26
2.42E−02
3′ss
Mel.



49918679-
49918679-
TTCGGGAGGTAT
TTCGGGAGGTAT









49919860
49919726
CAGAGTGCTCCA
TGCCAGGGAACA











TCTC (1062)
GACG (1063)











720
chr1:
chr1:
GTCCCGGCTTCC
GTCCCGGCTTCC
4
11
1.26
2.67E−02
exon
Mel.



46654652-
46655029-
CCCTACTCGCCT
CCCTACTCAGTG




skip




46655129
46655129
GGCTCAGAATCT
AAGAAGCCACCC











AACC (1064)
TCAG (1065)











721
chr3:
chr3:
CTTAAGCATATA
CTTAAGCATATA
28
68
1.25
2.24E−02
exon
Mel.



105397415-
105400454-
TTTAAAGGGTGA
TTTAAAGGGAGA




skip




105400567
105400567
AGATGCTTTTGA
TGTTTTTGATTC











TGCC (1066)
AGCC (1067)











722
chr3:
chr3:
CAGGAACAAGTA
CAGGAACAAGTA
2
6
1.22
4.97E−02
exon
Mel.



10023431-
10019130-
TCTGACAGAAAA
TCTGACAGTCAA




incl.




10028190
10028190
TATCTTTCAGGC
GTCCTAATTCGA











CTGG (1068)
AGCA (1069)











723
chr4:
chr4:
GAAGTTCTGAGG
GAAGTTCTGAGG
2
6
1.22
1.07E−02
3′ss
Mel.



88898249-
88898249-
AAAAGCAGAATG
AAAAGCAGCTTT









88901544
88901197
CTGTGTCCTCTG
ACAACAAATACC











AAGA (1070)
CAGA (1071)











724
chr7:
chr7:
ATCTCCCTCTTG
ATCTCCCTCTTG
2
6
1.22
1.94E−03
3′ss
Mel.



23313233-
23313233-
GTGTACAAATTG
GTGTACAAAAAA









23313672
23313683
TTTTCAGAAAAC
CACAAGGAATAC











ACAA (1072)
AACC (1073)











725
chr1:
chr1:
TGCGAGTACTGC
TGCGAGTACTGC
6
15
1.19
3.00E−03
exon
Mel.



214454770-
214454770-
TTCACCAGAAAG
TTCACCAGGAAA




skip




214488104
214478529
AAGATTGGCCCA
GAAGGATTGTCC











TGCA (1074)
AAAT (1075)











726
chr15:
chr15:
TCCAGAAAGTGA
TCCAGAAAGTGA
15
35
1.17
2.02E−04
exon
Mel.



101826006-
101826498-
AACTAAAATTTT
AACTAAAAGAGC




skip




101827112
101827112
AATCCAGGTGCT
GTCAGGAAGCAG











GGTT (1076)
AGAA (1077)











727
chr15:
chr15:
ACTCAGATGCCG
ACTCAGATGCCG
39
88
1.15
2.54E−04
3′ss
Mel.



74326871-
74326871-
AAAACTCGCCCT
AAAACTCGTGCA









74327483
74327512
CAGTCTGAGGTT
TGGAGCCCATGG











CTGT (748)
AGAC (749)











728
chrX:
chrX:
AGATTCTACAGA
AGATTCTACAGA
17
39
1.15
2.23E−02
exon
Mel.



15706981-
15706981-
TAAATCAGATTT
TAAATCAGCTGC




skip




15720904
15711085
CGGAAACTTCTG
ACTTAGTGCATT











GCAG (1078)
GGAA (1079)











729
chr3:
chr3:
TGGCTGGCTTCA
TGGCTGGCTTCA
40
90
1.15
1.67E−02
exon
Mel.



183703166-
183700795-
GTGGACCAAATT
GTGGACCAGCCT




incl.




183705557
183705557
TTCAGGATGGCT
TCATGGTGAAAC











GTAT (1080)
ACCT (1081)











730
chr16:
chr16:
CCCTGCTCATCA
CCCTGCTCATCA
19
40
1.04
9.38E−04
exon
Mel.



684797-
684956-
CCTACGGGGAAC
CCTACGGGCCCT




skip




685280
685280
CCAGAATGGGGG
ATGCCATCAATG











CTTC (1082)
GGAA (194)











731
chrX:
chrX:
CAAACACCTCTT
CAAACACCTCTT
11
23
1.00
2.44E−04
exon
Mel.



123224614-
123224614-
GATTATAACACG
GATTATAATCGG




incl.




123224703
123227867
CAGGTAACATGG
CGTGGCACAAGC











ATGT (468)
CTAA (457)











732
chr20:
chr20:
GGCAGCCACCAC
TGATAATTGGGC
10
21
1.00
2.87E−02
exon
Mel.



48700791-
48700791-
GGGCTCGGACAA
CTCCAAGAACAA




skip




48729643
48713208
TTTATGAAAACC
TTTATGAAAACC











GAAT (1083)
GAAT (1084)











733
chr19:
chr19:
ACCGCCCTGCAC
ACCGCCCTGCAC
7
15
1.00
2.95E−02
3′ss
Mel.



617870-
617849-
TGCTACAGGAGT
TGCTACAGGAAG









618487
618487
CCTCCGCTCTGC
GGCCTGACCTTC











CACA (1085)
GTCT (1086)











734
chr1:
chr1:
TCACAATTATAG
GTGCTATTAAAG
7
15
1.00
1.48E−02
exon
Mel.



220242774-
220242774-
GGGAAGAGCTCG
AAGAAGATCTCG




skip




220247308
220246191
TGGTCTGGGTTG
TGGTCTGGGTTG











ATCC (1087)
ATCC (1088)











735
chr1:
chr1:
CTCGTCTATGAT
CTCGTCTATGAT
6
13
1.00
3.26E−02
3′ss
Mel.



229431657-
229431657-
ATCACCAGATGC
ATCACCAGCCGA









229433266
229433228
CCGAATGCTAGC
GAAACCTACAAT











GAGC (1089)
GCGC (1090)











736
chr11:
chr11:
CAATGCCACAGG
CAATGCCACAGG
4
9
1.00
1.30E−02
3′ss
Mel.



57193182-
57193143-
GCAGGCTGGAAG
GCAGGCTGACTG









57193461
57193461
GCTGGGATGCAT
CAAAGCCCAGGA











GGGA (1091)
TGAG (1092)











737
chr11:
chr11:
TCAGAAGAGAAA
TCAGAAGAGAAA
3
7
1.00
3.02E−02
3′ss
Mel.



66105278-
66105360-
ATCGGATGACAG
ATCGGATGGACC









66105713
66105713
GCGGACCCACAG
TTGACCCTGCTG











GCCC (1093)
TTCA (1094)











738
chr7:
chr7:
TGACTGCCGCTT
CTAAAGCCTTCT
3
7
1.00
2.44E−02
exon
Mel.



44251203-
44250723-
TCTCTCAGGCCC
ATAAAACTGCCC




incl.




44251845
44251845
GGAAACAAAACT
GGAAACAAAACT











CATG (1095)
CATG (1096)











739
chr12:
chr12:
ATGCAGATACAC
ATGCAGATACAC
2
5
1.00
1.43E−02
exon
Mel.



57925889-
57926098-
AAAGCAAGCCAT
AAAGCAAGGTGC




skip




57926354
57926354
GCAGTTTGGTCA
ACCAGCTATATG











GCTC (1097)
AAAC (1098)











740
chr4:
chr4:
TACTGATCATAT
AAGAGTGCCAAA
2
5
1.00
2.55E−03
exon
Mel.



48853992-
48859382-
TGTCCAAGTCAA
AAAAGAAGTCAA




skip




48862741
48862741
AGTAAACAAGTA
AGTAAACAAGTA











TGGA (1099)
TGGA (1100)











741
chr2:
chr2:
TGTCATCCATTG
TGTCATCCATTG
1
3
1.00
2.77E−02
3′ss
Mel.



27604588-
27604672-
TGGAAGAGCCCC
TGGAAGAGCTGC









27604992
27604992
GAAACACAGCAG
TGGATCAGTGCC











AGCT (1101)
TGGC (1102)











742
chr6:
chr6:
TACCGGAAACCT
GCTGCCAAAGCC
1
3
1.00
4.97E−02
5′ss
Mel.



133136363-
133136227-
AGGAAAAGGCGC
TTAGACAAGCGC









133137599
133137599
CAAGCCCATCTT
CAAGCCCATCTT











TGTG (1103)
TGTG (1104)











743
chr12:
chr12:
GGGTGCAAAAGA
GGGTGCAAAAGA
0
1
1.00
8.93E−03
3′ss
Mel.



57032980-
57033091-
TCCTGCAGCCAT
TCCTGCAGGACT









57033763
57033763
TCCAGGTTGCTG
ACAAATCCCTCC











AGGT (283)
AGGA (284)











744
chr14:
chr14:
AGGATATCGGTT
AGGATATCGGTT
0
1
1.00
1.46E−02
3′ss
Mel.



50044571-
50050393-
TCATTAAGAAAG
TCATTAAGTTGG









50052667
50052667
ACCTGAGCTGTC
ACTAAATGCTCT











TTCC (1105)
TCCT (1106)











745
chr16:
chr16:
GCGGCGGGCAGT
GCGGCGGGCAGT
0
1
1.00
1.39E−02
3′ss
Mel.



85833358-
85833358-
GGCGGCAGGTGT
GGCGGCAGAATG









85834789
85834810
ACATTTTTATCT
TTGGCTACCAGG











TTCA (1107)
GTAT (1108)











746
chr19:
chr19:
TATCCAGCACTG
CCTGATTCTCCC
0
1
1.00
3.56E−02
exon
Mel.



35647877-
35646514-
ACCACATGGACA
CACCAGAGGACA




incl.




35648323
35648323
GACGTTGAAAGA
GACGTTGAAAGA











TACC (1109)
TACC (1110)











747
chr21:
chr21:
TTCATCATGGTG
TTCATCATGGTG
0
1
1.00
1.84E−02
3′ss
Mel.



27254101-
27254082-
TGGTGGAGCTCT
TGGTGGAGGTTG









27264033
27264033
CCTCTTGTTTTT
ACGCCGCTGTCA











CAGG (1111)
CCCC (1112)











748
chr21:
chr21:
TGAAATCAGAAA
TGAAATCAGAAA
0
1
1.00
3.04E−02
3′ss
Mel.



46271557-
46271542-
AAAATATGTTTA
AAAATATGGCCT









46275124
46275124
TTTTGTTTCAGG
GTTTAAAGAAGA











CCTG (1113)
AAAC (1114)











749
chr3:
chr3:
CAACGAGAACAA
CAACGAGAACAA
0
1
1.00
4.76E−04
3′ss
Mel.



101401353-
101401336-
GCTATCAGTTAC
GCTATCAGGGCT









101401614
101401614
TTTTACCCCACA
GCTAAGGAAGCA











GGGC (297)
AAAA (298)











750
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
1
1.00
4.92E−05
3′ss
Mel.



152022314-
152022314-
AATGGCAGCACC
AATGGCAGACAA









152024139
152024022
AACAGGTCCGCC
TGATTGAAGCTC











AAAT (344)
ACGT (345)











751
chr9:
chr9:
GCAAGGATATAT
GCAAGGATATAT
0
1
1.00
4.68E−04
3′ss
Mel.



86593213-
86593194-
AATAACTGCTGC
AATAACTGATTG









86593287
86593287
TTTATTTTTCCA
GTGTGCCCGTTT











CAGA (1115)
AATA (1116)











752
chr4:
chr4:
GAACTGCAAAGG
AGTGAATGTAGT
27
54
0.97
4.49E−02
exon
Mel.



169911479-
169911479-
CTTCAGAGGATT
TGCACCAGGATT




incl.




169919352
169923221
TGTACACACAGA
TGTACACACAGA











TATG (1117)
TATG (1038)











753
chrX:
chrX:
TTGGAGATCAGG
GATCTGGATTCT
21
42
0.97
2.52E−02
5′ss
Mel.



102940188-
102940188-
ACGCAAAGGTCA
CGTTTCAGGTCA









102942916
102941558
CCATCAGAAAAG
CCATCAGAAAAG











CTAA (1118)
CTAA (1119)











754
chr5:
chr5:
TGGAAGAGGCTA
TGGAAGAGGCTA
13
26
0.95
2.18E−02
exon
Mel.



137503767-
137504377-
CCTCTGGGGTCA
CCTCTGGGGTAA




skip




137504910
137504910
ATGAGAGTGAAA
CCCCCGGGACTT











TGGC (1120)
TGCC (1121)











755
chr13:
chr13:
TCTGGAGCCATA
TCTGGAGCCATA
11
22
0.94
4.45E−02
exon
Mel.



114291015-
114291015-
CGTGACAGTGAC
CGTGACAGAAAT




skip




114294434
114292132
CTGACCAACGGT
GGCTCAGGGAAC











GCAG (1122)
TGTT (1123)











756
chr16:
chr16:
CATCAAGCAGCT
CATCAAGCAGCT
11
22
0.94
4.68E−04
3′ss
Mel.



57473207-
57473246-
GTTGCAATGTTT
GTTGCAATCTGC









57474683
57474683
AGTCCCAGGAAG
CCACAAAGAATC











CACC (822)
CAGC (823)











757
chr22:
chr22:
CTGCAGTATCTG
CTGCAGTATCTG
28
52
0.87
1.79E−02
3′ss
Mel.



31724845-
31724910-
TAACCGAGGTCT
TAACCGAGGTTT









31731677
31731677
CCAGGCACCAGG
CTCCTCTGCCTC











AGCC (1124)
CTAC (1125)











758
chrX:
chrX:
ACTAATCTTCAG
CAAACACCTCTT
14
26
0.85
1.55E−02
exon
Mel.



123224814-
123224614-
CATGCCATTCGG
GATTATAATCGG




incl.




123227867
123227867
CGTGGCACAAGC
CGTGGCACAAGC











CTAA (456)
CTAA (457)











759
chr7:
chr7:
TGATTTCAAGTT
TGATGAGACTCC
56
100
0.83
5.42E−03
exon
Mel.



5028808-
5035213-
TGAACAAGGGGT
AGACAGAGGGGT




skip




5036240
5036240
TGGCATCTGCAC
TGGCATCTGCAC











ATCC (1126)
ATCC (1127)











760
chr8:
chr8:
AGCGAGCTCCTC
CCGGGGATTGCC
29
52
0.82
4.95E−02
5’ss
Mel.



146076780-
146076780-
AGCCTCAGGCAT
GGCGCCAGGCAT









146078756
146078377
CTGCATCTGGGA
CTGCATCTGGGA











CCGA (1128)
CCGA (1129)











761
chr5:
chr5:
AGTTTCTACTAG
AGTTTCTACTAG
7
13
0.81
3.69E−03
exon
Mel.



139909381-
139909381-
TCCAGTTGGTGA
TCCAGTTGGGTT




skip




139916922
139914946
CTCTCCTATTCC
ACCATCCATTGA











ATCT (1130)
CCCA (1131)











762
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
42
69
0.70
1.02E−05
3′ss
Mel.



67890660-
67890642-
GATAGATCTTCT
GATAGATCTGGC









67890765
67890765
TTTTCACATTAC
CTGAAGCACGAG











AGTG (444)
GACA (445)











763
chr22:
chr22:
GGAAAGGACAGC
TGAGGTGCCCTA
40
65
0.69
3.49E−02
exon
Mel.



42557364-
42557364-
AAGCACAGGTGA
AGCACAAGGTGA




incl.




42564614
42565852
GACTGTGGAGAT
GACTGTGGAGAT











GAGA (1132)
GAGA (1133)











764
chr6:
chr6:
AGTTGCATGTTG
AGTTGCATGTTG
4
7
0.68
3.75E−03
exon
Mel.



30587766-
30587766-
ACTTTAGGGAGT
ACTTTAGGAACG




skip




30592659
30590608
CTGTGTGAAGCA
TGAAGCTCTTGG











GCAC (1134)
AGCA (1135)











765
chr19:
chr19:
CCGCCCCCGTTC
CCGCCCCCGTTC
41
65
0.65
1.89E−02
3′ss
Mel.



2112966-
2112930-
CATCCACGGGGG
CATCCACGGACG









2113334
2113334
AGCTCAGTGTGA
AGTGTGAGGACG











ACAC (1136)
CCAA (1137)











766
chr16:
chr16:
TGGAGCCGAACA
TGGAGCCGAACA
8
13
0.64
4.20E−03
3′ss
Mel.



89960266-
89960266-
ACATCGTGCTCA
ACATCGTGGTTC









89961490
89961445
GCGATGCCTGCC
TGCTCCAGACGA











GCTT (1138)
GCCC (1139)











767
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
47
73
0.62
1.42E−03
3′ss
Mel.



75554088-
75554088-
TGCTCCAGTGGT
TGCTCCAGGTTC









75554298
75554313
TTCTCCCACAGG
CCGGCCCCCAAG











TTCC (466)
TCGC (467)











768
chr12:
chr12:
GCCTGGAAAGCT
GCCTGGAAAGCT
28
42
0.57
1.37E−03
3′ss
Mel.



6675490-
6675502-
ACCAAAAGGAGC
ACCAAAAGGGAT









6675694
6675694
TGTCCAGACAGC
CTCTGCAGGAGC











TGGT (1140)
TGTC (1141)











769
chr11:
chr11:
TGTTATTGTAGA
TGTTATTGTAGA
37
55
0.56
4.34E−05
3′ss
Mel.



85693031-
85693046-
TTCTGGGGGTGG
TTCTGGGGGCTT









85694908
85694908
ACTTCTCAAACC
TGATGAACTAGG











AACA (1142)
TGGA (1143)











770
chr2:
chr2:
GGGGACCAAGAA
GGGGACCAAGAA
59
86
0.54
2.26E−02
exon
Mel.



55530288-
55529208-
AAGCAGCATGGT
AAGCAGCACCAT




incl.




55535944
55535944
TGCACTGAAAAG
GAATGACCTGGT











ACTG (1144)
GCAG (1145)











771
chr12:
chr12:
CAAAAAAGACCA
CAAAAAAGACCA
13
19
0.51
2.94E−02
3′ss
Mel.



7043741-
7043741-
AAACTGAGGAAC
AAACTGAGCAGG









7044712
7044709
TCCCTCGGCCAC
AACTCCCTCGGC











AGTC (1146)
CACA (1147)











772
chr1:
chr1:
CCAAAGCAGAGA
CCAAAGCAGAGA
9
13
0.49
3.58E−02
3′ss
Mel



40209596-
40209596-
CCCAGGAGGTGT
CCCAGGAGGGAG









40211085
40211046
ACATGGACATCA
AGCCCATTGCTA











AGAT (1148)
AAAA (1149)











773
chr4:
chr4:
ACTGGGCTTCCA
ACTGGGCTTCCA
63
86
0.44
9.76E−04
exon
Mel.



54266006-
54266006-
CCGAGCAGAAAC
CCGAGCAGGAGA




incl.




54280781
54292038
AGCACTTCTTCT
TTACCTGGGGCA











CAGT (848)
ATTG (849)











774
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
61
83
0.44
3.34E−02
3′ss
Mel.



30310151-
30310133-
ATTTGAATCTCT
ATTTGAATAATC









30310420
30310420
TTCTCTCCCTTC
TTATCTTGGCTT











AGAA (479)
TGGA (480)











775
chr4:
chr4:
GCCGAATCACCT
ACTGGGCTTCCA
63
84
0.41
3.70E−03
exon
Mel.



54280889-
54266006-
GATCTAAGGAGA
CCGAGCAGGAGA




incl.




54292038
54292038
TTACCTGGGGCA
TTACCTGGGGCA











ATTG (1150)
ATTG (849)











776
chr1:
chr1:
ACGCCGCAAGTC
AGCACCCATGGG
66
87
0.39
2.24E−02
exon
Mel.



47024472-
47024472-
CTCCAGAGGAAC
TGCAGGGGGAAC




incl.




47025905
47027149
AGCAGCACAATG
AGCAGCACAATG











GACC (1151)
GACC (1152)











777
chr1:
chr1:
AACCAGTAACAA
AACCAGTAACAA
59
76
0.36
1.42E−02
3′ss
Mel.



150249040-
150249040-
CGGAACCTCAGA
CGGAACCTAGTC









150252050
150252053
GTCCAGATCTGA
CAGATCTGAACG











ACGA (1153)
ATGC (1154)











778
chr20:
chr20:
GAGACCGCGTGC
GAGACCGCGTGC
70
90
0.36
3.80E−03
3′ss
Mel.



62577996-
62577993-
GAGGACCGCAGC
GAGGACCGCAAT









62587612
62587612
AATGCAGAGTCC
GCAGAGTCCCTG











CTGG (1155)
GACA (1156)











779
chr1:
chr1:
GTCTCTGGCAAG
GTCTCTGGCAAG
78
100
0.35
3.86E−02
3′ss
Mel.



211836994-
211836970-
TAATCCAGAACT
TAATCCAGTAAT









211840447
211840447
TCTTAATCTTCC
TAAGAAGAAAGT











ATCC (1157)
TCAT (1158)











780
chr3:
chr3:
AAGCATGTAGAA
AAGCATGTAGAA
44
56
0.34
4.73E−02
3′ss
Mel.



133305566-
133305566-
AGCCGGAACAGG
AGCCGGAAGGAT









133306002
133306739
TACTTAAAATGA
AAAGAAATGGAG











ATGC (1159)
AAGA (1160)











781
chr1:
chr1:
AGCACCCATGGG
AGCACCCATGGG
69
87
0.33
4.36E−02
exon
Mel.



47025949-
47024472-
TGCAGGGGCAAG
TGCAGGGGGAAC




incl.




47027149
47027149
CTCCAGAAAAGG
AGCAGCACAATG











GACT (1161)
GACC (1152)











782
chr1:
chr1:
TCCACAAGAGCG
AGGCGGTGAGTG
46
58
0.33
4.32E−02
5′ss
Mel.



17330906-
17330906-
AGGAGGCGAAGC
TCGGACAGAAGC









17331201
17331186
GGGTGCTGCGGT
GGGTGCTGCGGT











ATTA (1162)
ATTA (1163)











783
chr1:
chr1:
TCCGCCCCACAG
GGCGGAGACATG
74
91
0.29
8.93E−03
5′ss
Mel.



155917806-
155917806-
TCCACGAGACTT
GACCAGAGACTT









155920089
155920059
TACCAGAATGCA
TACCAGAATGCA











GGAC (1164)
GGAC (1165)











784
chrl7:
chrl7:
TTGATCTTCGGC
TTGATCTTCGGC
72
84
0.22
4.78E−02
3′ss
Mel.



38080478-
38080473-
CCCACACGAACA
CCCACACGCAGA









38083736
38083736
GCAGAGAGGGGC
GAGGGGCAGCAG











AGCA (1166)
GATG (1167)











785
chr2:
chr2:
GAAAAACTTTCC
GAAAAACTTTCC
81
94
0.21
4.90E−02
3′ss
Mel.



242590750-
242590750-
AGCCATTGGGGG
AGCCATTGGAGG









242592926
242592721
GACAGGCCCCAC
TTGTCGGGACAT











CTCG (1168)
TTCA (1169)











786
chr9:
chr9:
GCGCTCGCCCGG
CCGCAGGATACC
76
86
0.18
2.12E−02
5′ss
Mel.



37422830-
37422802-
GCGGCAGACTGT
CGCCGAGGCTGT









37424841
37424841
GAGGTGGAGCAG
GAGGTGGAGCAG











TGGG (1170)
TGGG (1171)











787
chr20:
chr20:
CGGGACGACTTC
GCAGCATCTGCC
78
86
0.14
3.03E−02
exon
Mel.



32661672-
32661441-
TACGACAGGCTC
ATATACAGGCTC




incl.




32663679
32663679
TTCGACTACCGG
TTCGACTACCGG











GGCC (1172)
GGCC (1173)











788
chr3:
chr3:
ACTGAAGCAGCA
ACTGAAGCAGCA
92
98
0.09
3.80E−03
3′ss
Mel.



184084588-
184084588-
ACACGCCTCTCT
ACACGCCTGCTG









184085964
184085900
GCGTACGTGTCC
AGATTGAGAGCT











TATG (1174)
GCTG (1175)











789
chrl9:
chrl9:
CTGCCGGCGGAG
CTGCCGGCGGAG
93
99
0.09
7.19E−03
3′ss
Mel.



58817582-
58817582-
AATATAAGGAGA
AATATAAGGTGT









58823531
58823562
TGGACAAACCGT
GTGTGACCATGG











GTGG (1176)
AACG (1177)











790
chr5:
chr5:
CAACCTCTAAGA
CAACCTCTAAGA
97
99
0.03
2.75E−02
3′ss
Mel.



179225591-
179225576-
CTGGAGCGGTTC
CTGGAGCGTGGG









179225927
179225927
TTCTTCCGCAGT
AACATCGAGCAC











GGGA (1178)
CCGG (1179)









Certain splice variants are associated with more than one disease, and thus appear in Table 1 more than one time. In certain instances, splice variants associated with more than one cancer type may have different expression levels in each disease, so there may be more than one set of expression data for a given splice variant. Variants differentially expressed across all tested cancer types can be used to evaluate cells having SF3B1 neomorphic mutations in additional cancer types. Such variants are shown in the following rows of Table 1 (triplicates represent the same splice junction, measured in different cancer types): [13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28, 350, 573], [229, 762, 467], [240, 508, 767], [7, 356, 524], [76, 374, 596], [35, 547, 280], [84, 364, 571], [85, 564, 297], [24, 597, 296], [21, 372, 545], [36, 576, 407], [105, 423, 639], [62, 580, 447], [31, 279, 528], [235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72, 640], [48, 343, 554], [360, 65, 540], [178, 329, 750], [71, 265, 556], [15, 283, 530], [18, 267, 583], [129, 418, 622], [333, 25, 541], [247, 500, 774], [259, 5, 542], [152, 438, 615], [292, 1, 517], [81, 543, 443], [347, 70, 592], [91, 431, 617], [30, 298, 582], [17, 334, 602], [16, 276, 559], [51, 426, 548], [118, 401, 566], [83, 435, 574], and [269, 45, 546]. In certain embodiments, variants that are nonspecific to a particular cancer type can be chosen from the following rows of Table 1: [13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28, 350, 573], [240, 508, 767], [7, 356, 524], [84, 364, 571], [24, 597, 296], [21, 372, 545], [105, 423, 639], [62, 580, 447], [31, 279, 528], [235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72, 640], [360, 65, 540], [178, 329, 750], [71, 265, 556], [15, 283, 530], [18, 267, 583], [247, 500, 774], [152, 438, 615], [292, 1, 517], [81, 543, 443], [91, 431, 617], [30, 298, 582], [16, 276, 559], or [51, 426, 548].


Certain embodiments of the invention provide splice variants as markers for cancer. In certain circumstances, cancer cells with a neomorphic SF3B1 protein demonstrate differential expression of certain splice variants compared to cells without a neomorphic SF3B1 protein. The differential expression of one or more splice variants therefore may be used to determine whether a patient has cancer with a neomorphic SF3B1 mutation. In certain embodiments, the patient is also determined to have a cancer cell having a mutant SF3B1 protein. In these methods, one or more of the splice variants listed in Table 1 can be measured to determine whether a patient has cancer with a neomorphic SF3B1 mutation. In certain embodiments, one or more aberrant splice variants from Table 1 are measured. In other embodiments, one or more canonical splice variants are measured. Sometimes, both aberrant and canonical variants are measured.


In some embodiments, one or more aberrant splice variants selected from rows 260, 262, 263, 265, 266, 267, 272, 273, 275, 276, 277, 279, 281, 282, 286, 287, 288, 290, 294, 295, 296, 298, 299, 301, 302, 304, 305, 306, 308, 310, 312, 313, 315, 316, 318, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 335, 337, 339, 342, 346, 348, 349, 350, 352, 353, 354, 355, 356, 357, 358, 362, 363, 365, 366, 368, 369, 370, 372, 375, 377, 378, 379, 380, 381, 382, 383, 384, 387, 388, 389, 390, 391, 392, 393, 394, 397, 398, 400, 402, 403, 404, 405, 406, 413, 415, 416, 417, 419, 420, 421, 424, 425, 428, 429, 430, 431, 432, 433, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 454, 455, 456, 458, 459, 460, 461, 462, 464, 465, 468, 469, 471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 483, 484, 485, 486, 487, 488, 490, 491, 494, 496, 497, 498, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 513, 514, 515, or 516 of Table 1 can be measured in a patient suspected of having CLL. In additional embodiments, a patient suspected of having CLL can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 259, 269, 270, 271, 274, 278, 280, 282, 292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360, 361, 371, 373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 472, 479, 482, or 489. In additional embodiments, a patient suspected of having CLL can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 282, 292, 296, 302, 306, 330, 331, 343, 355, 360, 373, 378, 390, 391, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 463, 466, 468, 469, 470, 472, 479, 482, or 489. In still further embodiments, a patient suspected of having CLL can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 282, 296, 302, 306, 330, 331, 355, 378, 390, 391, 424, 425, 433, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, or 472.


In other embodiments, one or more aberrant splice variants selected from rows 2, 3, 4, 7, 9, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 27, 28, 30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 50, 52, 53, 54, 56, 57, 58, 61, 62, 63, 64, 66, 67, 68, 71, 72, 75, 77, 78, 79, 80, 81, 82, 84, 87, 88, 89, 90, 91, 92, 94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 146, 147, 150, 152, 154, 155, 156, 157, 159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 247, 249, 250, 251, 252, 253, 254, 255, 256, or 257 of Table 1 can be measured in a patient suspected of having breast cancer. In additional embodiments, a patient suspected of having breast cancer can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166. In additional embodiments, a patient suspected of having breast cancer can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, or 136. In still further embodiments, a patient suspected of having breast cancer can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 7, 9, 10, 66, 121, 135, or 136.


In further embodiments, one or more aberrant splice variants selected from rows 518, 519, 520, 521, 523, 524, 525, 526, 527, 528, 529, 531, 533, 534, 536, 537, 538, 539, 543, 544, 545, 549, 551, 552, 553, 555, 556, 557, 558, 559, 560, 561, 562, 563, 565, 567, 568, 569, 570, 572, 573, 575, 577, 578, 579, 580, 581, 582, 583, 584, 585, 588, 589, 590, 591, 593, 595, 597, 598, 599, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 623, 625, 627, 628, 629, 630, 632, 634, 635, 636, 637, 638, 640, 641, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 654, 657, 658, 659, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 680, 682, 683, 684, 685, 686, 687, 688, 689, 690, 692, 694, 696, 697, 698, 699, 700, 701, 702, 703, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 763, 764, 765, 766, 767, 768, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, or 790 of Table 1 can be measured in a patient suspected of having melanoma. In additional embodiments, a patient suspected of having melanoma can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655, 670, 679, 680, 727, 729, or 730. In additional embodiments, a patient suspected of having melanoma can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 522, 535, 554, 587, 601, 618, 639, 654, 670, 680, 727, or 730. In still further embodiments, a patient suspected of having melanoma can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 601, 618, 654, 670, 680, 727, or 730.


In some embodiments, one or more of the aberrant variants are selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1. In certain embodiments, a patient suspected of having cancer can be identified by measuring the amount of one or more of the aberrant variants selected from 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566. In various embodiments the cancer may be CLL, breast cancer, or melanoma, for example.


Additional methods include predicting or monitoring the efficacy of a treatment for cancer by measuring the level of one or more aberrant splice variants in samples obtained from patients before or during the treatment. For example, a decrease in the levels of one or more aberrant splice variants over the course of treatment may indicate that the treatment is effective. In other cases, the absence of a decrease or an increase in the levels of one or more aberrant splice variants over the course of treatment may indicate that the treatment is not effective and should be adjusted, supplemented, or terminated. In some embodiments, the splice variants are used to track and adjust individual patient treatment effectiveness.


Embodiments of the invention also encompass methods of stratifying cancer patients into different categories based on the presence or absence of one or more particular splice variants in patient samples or the detection of one or more particular splice variants at levels that are elevated or reduced relative to those in normal cell samples. Categories may be different prognostic categories, categories of patients with varying rates of recurrence, categories of patients that respond to treatment and those that do not, and categories of patients that may have particular negative side effects, and the like. According to the categories in which individual patients fall, optimal treatments may then be selected for those patients, or particular patients may be selected for clinical trials.


Embodiments also encompass methods of distinguishing cancerous cells with SF3B1 neomorphic mutations from normal cells by using the splice variants disclosed herein as markers. Such methods may be employed, for example, to assess the growth or loss of cancerous cells and to identify cancerous cells to be treated or removed. In some embodiments, the splice variants are measured in cancerous tissue having cells with a neomorphic SF3B1 mutation before and after anti-cancer treatment, for the purpose of monitoring the effect of the treatment on cancer progression.


In additional embodiments, administering an SF3B1 modulator to a cell, such as a cancer cell, can alter the differential expression of splice variants. Accordingly, the change in expression of one or more splice variants can be used to evaluate the effect of the SF3B1 modulator on the SF3B1 protein. In one embodiment, the effect of an SF3B1 modulator on a CLL cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 258-516 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 260, 262, 263, 265, 266, 267, 272, 273, 275, 276, 277, 279, 281, 282, 286, 287, 288, 290, 294, 295, 296, 298, 299, 301, 302, 304, 305, 306, 308, 310, 312, 313, 315, 316, 318, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 335, 337, 339, 342, 346, 348, 349, 350, 352, 353, 354, 355, 356, 357, 358, 362, 363, 365, 366, 368, 369, 370, 372, 375, 377, 378, 379, 380, 381, 382, 383, 384, 387, 388, 389, 390, 391, 392, 393, 394, 397, 398, 400, 402, 403, 404, 405, 406, 413, 415, 416, 417, 419, 420, 421, 424, 425, 428, 429, 430, 431, 432, 433, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 454, 455, 456, 458, 459, 460, 461, 462, 464, 465, 468, 469, 471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 483, 484, 485, 486, 487, 488, 490, 491, 494, 496, 497, 498, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 513, 514, 515, or 516 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 259, 269, 270, 271, 274, 278, 280, 282, 292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360, 361, 371, 373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 472, 479, 482, or 489. In additional embodiments, the one or more splice variants are chosen from rows 282, 292, 296, 302, 306, 330, 331, 343, 355, 360, 373, 378, 390, 391, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 463, 466, 468, 469, 470, 472, 479, 482, or 489 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 282, 296, 302, 306, 330, 331, 355, 378, 390, 391, 424, 425, 433, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, or 472 of Table 1.


In certain embodiments, the effect of an SF3B1 modulator on a breast cancer cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 1-257 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 2, 3, 4, 7, 9, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 27, 28, 30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 50, 52, 53, 54, 56, 57, 58, 61, 62, 63, 64, 66, 67, 68, 71, 72, 75, 77, 78, 79, 80, 81, 82, 84, 87, 88, 89, 90, 91, 92, 94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 146, 147, 150, 152, 154, 155, 156, 157, 159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 247, 249, 250, 251, 252, 253, 254, 255, 256, or 257 of Table 1. In additional embodiments, the one or more splice variants are chosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, or 136 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 7, 9, 10, 66, 121, 135, or 136 of Table 1.


In a further embodiment, the effect of an SF3B1 modulator on a melanoma cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 517-790 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 518, 519, 520, 521, 523, 524, 525, 526, 527, 528, 529, 531, 533, 534, 536, 537, 538, 539, 543, 544, 545, 549, 551, 552, 553, 555, 556, 557, 558, 559, 560, 561, 562, 563, 565, 567, 568, 569, 570, 572, 573, 575, 577, 578, 579, 580, 581, 582, 583, 584, 585, 588, 589, 590, 591, 593, 595, 597, 598, 599, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 623, 625, 627, 628, 629, 630, 632, 634, 635, 636, 637, 638, 640, 641, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 654, 657, 658, 659, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 680, 682, 683, 684, 685, 686, 687, 688, 689, 690, 692, 694, 696, 697, 698, 699, 700, 701, 702, 703, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 763, 764, 765, 766, 767, 768, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, or 790 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655, 670, 679, 680, 727, 729, or 730 of Table 1. In additional embodiments, the one or more splice variants are chosen from rows 519, 521, 522, 535, 554, 587, 601, 618, 639, 654, 670, 680, 727, or 730 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 519, 521, 601, 618, 654, 670, 680, 727, or 730 of Table 1.


In some embodiments, the effect of an SF3B1 modulator on a cancer cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the aberrant variants selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1. In various embodiments, the cancer cell may be a CLL cell, a breast cancer cell, or a melanoma cell, for example.


The specific splice variants that are useful for demonstrating the effect of an SF3B1 modulator on one type of cancer cell may not be useful for demonstrating an effect of the modulator on another type of cancer cell. Aberrant splice variants that are appropriate for revealing such effects in particular cancer cells will be apparent from the description and examples provided herein.


In some embodiments, aberrant splice variants that are present at elevated levels in a cell having a neomorphic SF3B1 protein are used as markers. In other embodiments, splice variants that have reduced levels in a cell having a neomorphic SF3B1 protein are used as markers. In some embodiments, more than one splice variant will be measured. When more than one splice variant is used, they may all have elevated levels, all have reduced levels, or a mixture of splice variants with elevated and reduced levels may be used. In certain embodiments of the methods described herein, more than one aberrant splice variant is measured. In other embodiments, at least one aberrant and at least one canonical splice variant is measured. In some cases, both an aberrant and canonical splice variant associated with a particular genomic location will be measured. In other circumstances, a measured canonical splice variant will be at a different genomic location from the measured aberrant splice variant(s).


Before performing an assay for splice variants in a cell, one may determine whether the cell has a mutant SF3B1 protein. In certain embodiments, the assay for splice variants is performed if the cell has been determined to have a neomorphic SF3B1 mutant protein.


Samples


Cell samples can be obtained from a variety of biological sources. Exemplary cell samples include but are not limited to a cell culture, a cell line, a tissue, oral tissue, gastrointestinal tissue, an organ, an organelle, a biological fluid, a blood sample, a urine sample, a skin sample, and the like. Blood samples may be whole blood, partially purified blood, or a fraction of whole or partially purified blood, such as peripheral blood mononucleated cells (PBMCs). The source of a cell sample may be a solid tissue sample such as a tissue biopsy. Tissue biopsy samples may be biopsies from breast tissue, skin, lung, or lymph nodes. Samples may be samples of bone marrow, including bone marrow aspirates and bone marrow biopsies.


In certain embodiments, the cells are human cells. Cells may be cancer cells, for example hematological cancer cells or solid tumor cells. Hematological cancers include chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, acute monocytic leukemia, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, and multiple myeloma. Solid tumors include carcinomas, such as adenocarcinomas, and may be selected from breast, lung, liver, prostate, pancreatic, colon, colorectal, skin, ovarian, uterine, cervical, or renal cancers. Cell samples may be obtained directly from a patient or derived from cells obtained from a patient, such as cultured cells derived from a biological fluid or tissue sample. Samples may be archived samples, such as kryopreserved samples, of cells obtained directly from a subject or of cells derived from cells obtained from a patient.


In certain embodiments, cells are obtained from patients suspected of having cancer. The patients may show signs and symptoms of cancer, such as one or more common symptoms of CLL, which include enlarged lymph nodes, liver, or spleen, higher-than-normal white blood cell counts, recurring infections, loss of appetite or early satiety, abnormal bruising, fatigue, and night sweats. In additional embodiments, the cells have a mutant SF3B1 protein.


Cell samples described herein may be used in any of the methods presently disclosed.


Detection of Splice Variants


Certain embodiments of the methods described herein involve detection or quantification of splice variants. A variety of methods exists for detecting and quantifying nucleic acids, and each may be adapted for detection of splice variants in the described embodiments. Exemplary methods include an assay to quantify nucleic acid such as nucleic acid barcoding, nanoparticle probes, in situ hybridization, microarray, nucleic acid sequencing, and PCR-based methods, including real-time PCR (RT-PCR).


Nucleic acid assays utilizing barcoding technology such as NanoString® assays (NanoString Technologies) may be performed, for example, as described in U.S. Pat. Nos. 8,519,115; 7,919,237; and in Kulkarni, M. M., 2011, “Digital Multiplexed Gene Expression Analysis Using the NanoString nCounter System.” Current Protocols in Molecular Biology, 94:25B.10.1-25B.10.17. In an exemplary assay, a pair of probes is used to detect a particular nucleotide sequence of interest, such as a particular splice variant of interest. The probe pair consists of a capture probe and a reporter probe and that each include a sequence of from about 35 to 50 bases in length that is specific for a target sequence. The capture probe includes an affinity label such as biotin at its 3′ end that provides a molecular handle for surface-attachment of target mRNAs for digital detection, and the reporter probe includes a unique color code at its 5′ end that provides molecular barcoding of the hybridized mRNA target sequence. Capture and reporter probe pairs are hybridized to target mRNA in solution, and after excess probes are removed, the target mRNA-probe complexes are immobilized in an nCounter® cartridge. A digital analyzer acquires direct images of the surface of the cartridge to detect color codes corresponding to specific mRNA splice variant sequences. The number of times a color-coded barcode for a particular splice variant is detected reflects the levels of a particular splice variant in the mRNA library. For the detection of splice variants, either the capture or the reporter probe may span a given splice variant's exon-exon or intron-exon junction. In other embodiments, one or both of the capture and reporter probes' target sequences correspond to the terminal sequences of two exons at an exon-exon junction or to the terminal sequences of an intron and an exon at an intron-exon junction, whereby one probe extends to the exon-exon or intron-exon junction, but does not span the junction, and the other probe binds a sequence that begins on opposite side of the junction and extends into the respective exon or intron.


In exemplary PCR-based methods, a particular splice variant may be detected by specifically amplifying a sequence that contains the splice variant. For example, the method may employ a first primer specifically designed to hybridize to a first portion of the splice variant, where the splice variant is a sequence that spans an exon-exon or intron-exon junction at which alternative splicing occurs. The method may further employ a second opposing primer that hybridizes to a segment of the PCR extension product of the first primer that corresponds to another sequence in the gene, such as a sequence at an upstream or downstream location. The PCR detection method may be quantitative (or real-time) PCR. In some embodiments of quantitative PCR, an amplified PCR product is detected using a nucleic acid probe, wherein the probe may contain one or more detectable labels. In certain quantitative PCR methods, the amount of a splice variant of interest is determined by detecting and comparing levels of the splice variant to an appropriate internal control.


Exemplary methods for detecting splice variants using an in situ hybridization assay such as RNAscope® (Advanced Cell Diagnostics) include those described by Wang, F., et al., “RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues,” J. Mol. Diagn. 2012 January; 14(1):22-9. RNAscope® assays may be used to detect splice variants by designing a pair of probes that targets a given splice variant, and are hybridized to target RNA in fixed and permeabilized cells. Target probes are designed to hybridize as pairs which, when hybridized to the target sequence, create a binding site for a preamplifier nucleic acid. The preamplifier nucleic acid, in turn, harbors multiple binding sites for amplifier nucleic acids, which in turn contain multiple binding sites for a labeled probe carrying a chromogenic or fluorescent molecule. In some embodiments, one of the RNAscope® target probes spans a given splice variant's exon-exon or intron-exon junction. In other embodiments, the target probes' target sequences correspond to the terminal sequences of two exons at an exon-exon junction or to the terminal sequences of an intron and an exon at an intron-exon junction, whereby one probe in the target probe pair extends to the exon-exon or intron-exon junction, but does not span the junction, and the other probe binds a sequence beginning on opposite side of the junction and extending into the respective exon or intron.


Exemplary methods for detecting splice variants using nanoparticle probes such as SmartFlare™ (Millipore) include those described in Seferos et al., “Nano-flares: Probes for Transfection and mRNA Detection in Living Cells,” J. Am. Chem. Soc. 129(50):15477-15479 (2007) and Prigodich, A. E., et al., “Multiplexed Nanoflares: mRNA Detection in Live Cells,” Anal. Chem. 84(4):2062-2066 (2012). SmartFlare™ detection probes may be used to detect splice variants by generating gold nanoparticles that are modified with one or more nucleic acids that include nucleotide recognition sequences that (1) are each complementary to a particular splice variant to be detected and (2) are each hybridized to a complementary fluorophore-labeled reporter nucleic acid. Upon uptake of the probe by a cell, a target splice variant sequence may hybridize to the one or more nucleotide recognition sequences and displace the fluorophore-labeled reporter nucleic acid. The fluorophore-labeled reporter nucleic acid, whose fluorophore had been quenched due to proximity to the gold nanoparticle surface, is then liberated from the gold nanoparticle, and the fluorophore may then be detected when free of the quenching effect of the nanoparticle. In some embodiments, nucleotide recognition sequences in the probes recognize a sequence that spans a given splice variant's exon-exon or intron-exon junction. In some embodiments, nucleotide recognition sequences in the probes recognize a sequence that is only on one side of the splice variant's exon-exon or intron-exon junction, including a sequence that terminates at the junction and a sequence that terminates one or more nucleotides away from the junction.


Exemplary methods for detecting splice variants using nucleic acid sequencing include RNA sequencing (RNA-Seq) described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012); and van Dijk et al., “Ten years of next-generation sequencing technology.” Trends Genet 30(9):418-26 (2014). In some embodiments, high-throughput sequencing, such as next-generation sequencing (NGS) technologies, may be used to detected splice variants. For example, the method may employ commercial sequencing platforms available for RNA-Seq, such as, e.g., Illumina, SOLID, Ion Torrent, and Roche 454. In some embodiments, the sequencing method may include pyrosequencing. For example, a sample may be mixed with sequencing enzymes and primer and exposed to a flow of one unlabeled nucleotide at a time, allowing synthesis of the complementary DNA strand. When a nucleotide is incorporated, pyrophosphate is released leading to light emission, which is monitored in real time. In some embodiments, the sequencing method may include semiconductor sequencing. For example, proton instead of pyrophosphate may be released during nucleotide incorporation and detected in real time by ion sensors. In some embodiments, the method may include sequencing with reversible terminators. For example, the synthesis reagents may include primers, DNA polymerase, and four differently labelled, reversible terminator nucleotides. After incorporation of a nucleotide, which is identified by its color, the 3′ terminator on the base and the fluorophore are removed, and the cycle is repeated. In some embodiments, the method may include sequencing by ligation. For example, a sequencing primer may be hybridized to an adapter, with the 5′ end of the primer available for ligation to an oligonucleotide hybridizing to the adjacent sequence. A mixture of octamers, in which bases 4 and 5 are encoded by one of four color labels, may compete for ligation to the primer. After color detection, the ligated octamer may be cleaved between position 5 and 6 to remove the label, and the cycle may be repeated. Thereby, in the first round, the process may determine possible identities of bases in positions 4, 5, 9, 10, 14, 15, etc. The process may be repeated, offset by one base using a shorter sequencing primer, to determine positions 3, 4, 8, 9, 13, 14, etc., until the first base in the sequencing primer is reached.


Other nucleic acid detection and analytical methods that also distinguish between splice variants of a given exon-exon or intron-exon junction in a gene by identifying the nucleotide sequence on both sides of the junction may be utilized to detect or quantify the splice variants disclosed herein. For example, splice variants of an exon-exon junction may be detected by primer extension methods in which a primer that binds to one exon is extended into the exon on the other side of the junction according to the sequence of that adjacent exon. See, for example, McCullough, R. M., et al., “High-throughput alternative splicing quantification by primer extension and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,” Nucleic Acids Research, 2005 Jun. 20; 33(11):e99; and Milani, L., et al., “Detection of alternatively spliced transcripts in leukemia cell lines by minisequencing on microarrays,” Clin. Chem. 52: 202-211 (2006). Detection of variants on a large scale may be performed using expression microarrays that carry exon-exon or intron-exon junction probes, as described, for example, in Johnson, J. M. et al., “Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays,” Science 302: 2141-2144 (2003); and Modrek, B., et al., “Genome-wide detection of alternative splicing in expressed sequences of human genes,” Nucleic Acids Res 29: 2850-2859 (2001).


Various embodiments include reagents for detecting splice variants of the invention. In one example, reagents include NanoString® probes designed to measure the amount of one or more of the aberrant splice variants listed in Table 1. Probes for nucleic acid quantification assays such as barcoding (e.g. NanoString®), nanoparticle probes (e.g. SmartFlare™), in situ hybridization (e.g. RNAscope®), microarray, nucleic acid sequencing, and PCR-based assays may be designed as set forth above.


In these exemplary methods or in other methods for nucleic acid detection, aberrant splice variants may be identified using probes, primers, or other reagents which specifically recognize the nucleic acid sequence that is present in the aberrant splice variant but absent in the canonical splice variant. In other embodiments, the aberrant splice variant is identified by detecting the sequence that is specific to the aberrant splice variant in the context of the junction in which it occurs, i.e., the unique sequence is flanked by the sequences which are present on either side of the splice junction in the canonical splice variant. In such cases, the portion of the probe, primer, or other detection reagent that specifically recognizes its target sequence may have a length that corresponds to the length of the aberrant sequence or to or a portion of the aberrant sequence. In other embodiments, the portion of the probe, primer, or other detection reagent that specifically recognizes its target sequence may have a length that corresponds to the length of the aberrant sequence plus the length of a chosen number of nucleotides from one or both of the sequences which flank the aberrant sequence at the splice junction. Generally, the probe or primer should be designed with a sufficient length to reduce non-specific binding. Probes, primers, and other reagents that detect aberrant or canonical splice variants may be designed according to the technical features and formats of a variety of methods for detection of nucleic acids.


SF3B1 Modulators


A variety of SF3B1 modulating compounds are known in the art, and can be used in accordance with the methods described herein. In some embodiments, the SF3B1 modulating compound is a pladienolide or pladienolide analog. A “pladienolid analog” refers to a compound which is structurally related to a member of the family of natural products known as the pladienolides. Plandienolides were first identified in the bacteria Streptomyces platensis (Sakai, Takashi; Sameshima, Tomohiro; Matsufuji, Motoko; Kawamura, Naoto; Dobashi, Kazuyuki; Mizui, Yoshiharu. “Pladienolides, New Substances from Culture of Streptomyces platensis Mer-11107. I. Taxonomy, Fermentation, Isolation and Screening.” The Journal of Antibiotics. 2004, Vol. 57, No. 3). One of these compounds, pladienolide B, targets the SF3B spliceosome to inhibit splicing and alter the pattern of gene expression (Kotake et al., “Splicing factor SF3b as a target of the antitumor natural product pladienolide”, Nature Chemical Biology 3:570-575 [2007]). Certain pladienolide B analogs are described in WO 2002/060890; WO 2004/011459; WO 2004/011661; WO 2004/050890; WO 2005/052152; WO 2006/009276; and WO 2008/126918.


U.S. Pat. Nos. 7,884,128 and 7,816,401, both entitled “Process for Total Synthesis of Pladienolide B and Pladienolide D,” describe methods for synthesizing pladienolide B and D. Synthesis of pladienolide B and D may also be performed using methods described in Kanada et al., “Total Synthesis of the Potent Antitumor Macrolides Pladienolide B and D,” Angew. Chem. Int. Ed. 46:4350-4355 (2007). Kanada et al., U.S. Pat. No. 7,550,503, and International Publication No. WO 2003/099813 (WO '813), entitled “Novel Physiologically Active Substances,” describe methods for synthesizing E7107 (Compound 45 of WO '813) from pladienolide D (11107D of WO '813). In some embodiments, the SF3B1 modulator is pladienolide B. In other embodiments, the SF3B1 modulator is pladienolide D. In further embodiments, the SF3B1 modulator is E7107.


In some embodiments, the SF3B1 modulator is a compound described in U.S. application Ser. No. 14/710,687, filed May 13, 2015, which is incorporated herein by reference in its entirety. In some embodiments, the SF3B1 modulating compound is a compound having one of formulas 1-4 as set forth in Table 2. Table 2. Exemplary SF3B1 modulating compounds.












Compound Structure


















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1







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2







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3







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4









The methods described herein may be used to evaluate known and novel SF3B1 modulating compounds.


Methods of Treatment


Various embodiments of the invention include treating a patient diagnosed with cancer using an SF3B1 modulator. In certain instances, cancer cells from the patient have been determined to have a mutant SF3B1 protein. Specific SF3B1 mutants include E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. In certain embodiments, SF3B1 mutants are chosen from K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In additional embodiments, the cancer cells have been tested to measure the amount of one or more splice variants selected from Table 1. Specific splice variants associated with neomorphic SF3B1 mutations are shown in Table 1 and described in the section on splice variants above.


In certain embodiments, a cancer patient determined to have a mutant SF3B1 protein is treated with an SF3B1 modulator as described in U.S. application Ser. No. 14/710,687, filed May 13, 2015.


EXAMPLES
Example 1: SF3B1 Mutations Induce Abnormal Splicing in a Lineage-Specific Manner

To investigate splicing alterations associated with SF3B1 mutations (“SF3B1MUT”) across multiple tumor types, an RNA-Seq quantification and differential splicing pipeline was developed and used to analyze RNA-Seq profiles from the following samples:


all SF3B1MUT samples in The Cancer Genome Atlas (TCGA; from 81 patients in all, representing 16 cancer types), and 40 wild type SF3B1 (SF3B1WT) samples from each of the breast cancer (20) and melanoma (20) cohorts in TCGA,


seven SF3B1MUT and seven SF3B1WT CLL patient samples obtained from the Lymphoma/Myeloma Service in the Division of Hematology/Oncology at the New York Weill Cornell Medical Center.


RNA-Seq Quantification Methods


Splice junctions were quantified directly from alignments (BAM files) to facilitate discovery of unannotated splice variants. For internally generated RNA-Seq data, reads were aligned to the human reference genome hg19 (GRCh37) by MapSplice and quantified by RSEM against the TCGA GAF 2.1 isoform and gene definition, emulating the TCGA “RNASeqV2” pipeline. Splice junction counts generated by MapSplice were used for downstream processing. For TCGA RNA-Seq data, comprehensive splice junction counts generated by MapSplice were not available; instead TCGA “Level 3” splice junction data reports mapped read counts for a predefined set of splice junctions from reference transcriptomes. To reconstruct genome-wide splice junction counts comparable to internally-generated RNA-Seq samples, raw RNA-Seq alignments (BAM files) were obtained from CGHub and any reads that span across a potential splice junction were directly counted. RSEM-estimated gene expression read counts were gathered directly from the TCGA RNA-SeqV2 Level 3 data matrices.


Because MapSplice only provides exon-exon junction counts, estimates of read counts spanning each intron-exon junction were required for identification of intron-retention splice variants. For every splice junction in each BAM file, reads with at least a 3-bp overhang across each of the 3′ and 5′ intron-exon junctions were counted.


For all manipulation of spliced reads within BAM files, a custom Python module “splicedbam” was used, which uses the “pysam” extension of samtools (Li, H., et al., “The Sequence Alignment/Map format and SAMtools.” Bioinformatics, 2009 Aug. 15; 25(16):2078-9).


In some instances, splice junctions had very low counts, occasionally due to sequencing and alignment errors. Therefore, only splice junctions that had at least a total of 10 counts on average from either SF3B1WT or SF3B1MUT cohorts were included in downstream analyses.


Differential Splicing Detection Methods


In order to detect differential usage of a splice variant in one cohort relative to another, independent of gene expression changes and pre-defined alternative splicing models, a computational differential splicing pipeline was developed that converts splice junction counts into percentages of junction usage at splice sites with multiple possible junctions. The percentage of junction usage is a measurement of the occurrence of one splice variant relative to all other splice variants that share the same splice site. For instance, a splice variant with an alternative 3′ splice site must share its 5′ splice site with another splice variant. Therefore, for each shared splice site, the raw counts of each splice variant were divided by the total counts of all splice variants that utilize the shared splice site in order to derive a ratio. This ratio was then multiplied by 100 to convert it to a percentage. For each sample, the sum of all of the percentages of splice variants that share the same splice site will equal 100. The transformation of raw counts of each splice variant into a percentage of all splice variants sharing a splice site is itself a normalization to reduce the effect of gene expression changes. The percentages for canonical and aberrant junctions are listed in Table 1 as “Avg WT %” and “Avg Ab. %,” respectively. Differences between these percentages were assessed for statistical significance by using the moderated t-test defined in the Bioconductor's limma package. The statistical p-values were corrected into q values using the Benjamini-Hochberg procedure, and listed as “FDR Q-Values” in Table 1. Any splice variant that satisfied a q value of less than or equal to 0.05 was considered statistically significant.


The conversion of raw junction counts into percentage junction usage can introduce noise in some instances, i.e., when a gene in which a splice variant occurs is expressed in one cohort but has very low expression or is not expressed at all in another cohort. To address this, an additional filtering step was introduced. For each up-regulated splice variant in an SF3B1MUT sample that satisfies the above q value threshold, its corresponding canonical splice variant must be down-regulated in the SF3B1MUT sample and also must also satisfy the q value threshold for the up-regulated splice variant to be considered an aberrant splice variant.


Identification of Aberrant Splice Variants in Neomorphic SF3B1MUT Patient Samples


Initially, this framework was applied to a subset of known SF3B1MUT cancers or wild-type counterparts from The Cancer Genome Atlas (TCGA; luminal A primary breast cancer: 7 SF3B1K700E and 20 SF3B1WT; metastatic melanoma: 4 SF3B1MUT; and 20 SF3B1WT) and internally generated 7 SF3B1MUT and 7 SF3B1WT CLL patient samples. This analysis revealed 626 aberrant splice junctions to be significantly upregulated in SF3B1MUT compared to SF3B1WT. The vast majority of aberrant splicing events use an alternative 3′ss (see Table 1, “Event” column).


The computational screening of aberrant splicing events revealed a pattern of tumor-specific splicing events in breast cancer, melanoma and CLL in neomorphic SF3B1MUT samples (Table 1). In addition, a set of tumor-non-specific events (i.e., splicing events found in at least two tumor types) was observed. Some splice variants of genes with tumor-specific splicing events occur in genes with higher mRNA expression, indicating that some of the observed tumor-specific splicing results from gene expression differences (FIG. 2).


To characterize the effect of aberrant splicing in all SF3B1 variants across cancer types, RNA-Seq data for the remaining 70 SF3B1MUT patients from 14 cancer types in TCGA were quantified, and an unsupervised clustering analysis was done using all 136 samples. This clustering separated splicing events associated with neomorphic SF3B1 mutants from those associated with wild-type SF3B1 or non-neomorphic SF3B1 mutants. For example, splicing patterns associated with neomorphic SF3B1 mutants were observed in breast cancer (SF3B1K666E,sF3B12626D), lung adenocarcinoma (SF3B1K741N, SF3B1G740V), and bladder cancer (SF3B1R625C) patient samples, as splicing events in these samples clustered with those in SF3B1K700E neomorphic samples, whereas the splicing profiles for other SF3B1 mutant samples were similar to those of SF3B1′ samples of the same tumor type. A listing of SF3B1 mutants whose splicing profiles clustered with those of neomorphic SF3B1 mutants is provided in Table 3, column 1. Additional SF3B1 mutations that are predicted to be neomorphic are listed in Table 3, column 2. A schematic diagram showing the locations of all mutations provided in Table 3 is shown in FIG. 3.









TABLE 3







Select SF3B1 mutations








SF3B1 Mutations with Splicing



Profiles Clustering with
Predicted Neomorphic SF3B1


Neomorphic SF3B1 Mutations
Mutations





K700E
K666Q


K666N
K666M


R625C
H662D


G742D
D781G


R625H
I704F


E622D
I704N


H662Q
V701F


K666T
R625P


K666E
R625G


K666R
N626D


G740E
H662Y


Y623C
N626S


T663I
G740R


K741N
N626I


N626Y
N626H


T663P
V701I


H662R
R625S


G740V
K741T


D781E
K741Q


R625L
I704V



I704S



E622V



Y623S



Y623H



V701A



K666S



H662L



G740K



E622Q



E622K



D781N









Example 2: Validation of Aberrant Splice Variants in Cell Lines

Aberrant splicing in cell line models was analyzed by collecting RNA-Seq profiles for a panel of cell lines with endogenous SF3B1 neomorphic mutations (pancreatic adenocarcinoma Panc 05.04: SF3B1Q699H/K700E double mutant; metastatic melanoma Colo829: SF3B1P718L; and lung cancer NCI-H358: SF3B1A745V; obtained from the American Type Culture Collection [ATCC] or RIKEN BioResource Center and cultured as instructed) and from several SF3B1WT cell lines from either the same tumor types (pancreatic adenocarcinoma Panc 10.05, HPAF-II, MIAPaCa-2, Panc04.03, PK-59, lung cancer NCI-H358, NCI-H1792, NCI-H1650, NCI-H1975, NCI H1838) or normal control cells of the same patient (Epstein-Barr virus [EBV]-transformed B lymphoblast colo829BL). RNA-Seq profiles were also collected from isogenic pre B-cell lines (Nalm-6) engineered via AAV-mediated homology to express SF3B1K700E (Nalm-6 SF3B1K700E) or a synonymous mutation (Nalm-6 SF3B1K700K). The isogenic cell lines Nalm-6 SF3B1K700E and Nalm-6 SF3B1K700K, generated at Horizon Discovery, were cultured in presence of Geneticin (0.7 mg/ml, Life Technologies) for selection. All RNA-Seq analysis was performed using the same pipeline described for patient samples in Example 1. Unsupervised clustering of cell lines using the aberrant splice junctions identified in patients resulted in clear segregation of Panc 05.04 and Nalm-6 SF3B1K700E from wild-type and other SF3B1-mutant cells.


A NanoString® assay was developed to quantify aberrant and canonical splice variants and was validated using the same cell panel. For the NanoString® assay, 750 ng of purified total RNA was used as template for the nCounter® (NanoString Technologies®) expression assay using a custom panel of NanoString® probes. The sample preparation was set up as recommended (NanoString® Technologies protocol no. C-0003-02) for an overnight hybridization at 65° C. The following day, samples were processed through the automated nCounter® Analysis System Prep Station using the high sensitivity protocol (NanoString® Technologies protocol no. MAN-00029-05) followed by processing through the nCounter® Analysis System Digital Analyzer (protocol no. MAN-00021-01) using 1150 FOVs for detection. Data was downloaded and analyzed for quality control metrics and normalization using the nSolver™ Analysis Software (NanoString Technologies®). The data was first normalized for lane-to-lane variation using the positive assay controls provided by the manufacturer (NanoString® positive controls A-F [containing in vitro transcribed RNA transcripts at concentrations of 128 fM, 32 fM, 8 fM, 2 fM, 0.5 fM, and 0.125 fM, each pre-mixed with NanoString® Reporter CodeSet probes])). Any samples with normalization factors <0.3 and >3 were not considered for further analysis. This was followed by content normalization using the geo-mean of GAPDH, EEF1A1 and RPLP0. All samples were within the recommended 0.1-10 normalization factor range. Each normalized value was then checked to ensure that it was at least two standard deviations higher than the average of background signal recorded for that lane. Any value below that was considered below detection limit. These normalized values were taken for further bioinformatics and statistical analysis.


As observed in the RNA-Seq analysis, only the Panc 05.04 and isogenic Nalm-6 SF3B1K700E cell lines showed clear presence of aberrant splicing (FIG. 4).


Analysis of SF3B1 Mutant SF3B1Q699H


The Panc 05.04 cell line carries the neomorphic mutation SF3B1K700E and an additional mutation at position 699 (SF3B1Q699H). To evaluate the functional relevance of this second mutation, SF3B1Q699H and SF3B1K700E mutant SF3B1 proteins were expressed alone or in combination in 293FT cells (FIG. 5) for analysis of RNA by NanoString®. To express the mutants in 293FT cells, mammalian expression plasmids were generated using the Gateway technology (Life Technologies). First, the HA-tag mxSF3B1 wild-type (Yokoi, A. et al. “Biological validation that SF3b is a target of the antitumor macrolide pladienolide.” FEBS J. 278:4870-4880 [2011]) was cloned by PCR into the pDONR221, then the mutations were introduced using the site-directed mutagenesis kit (QuikChange II XL, Agilent). LR reaction was performed to clone all the HA-tag mxSF3B1 wild-type and mutants into the pcDNA-DEST40 (Life Technologies). 293FT cells (Life Technologies), cultured according to the manufacturer's instructions, were seeded on 6 wells/plate and transfected with generated plasmid using Fugene (Roche). One μg of DNA per pcDNA-DEST40 HA-mxSF3B1 construct was used for each transient transfection, generated in triplicates. Forty-eight hours after transfection, cells were collected to isolate protein and RNA for western blot and NanoString® analysis, respectively. Protein extracts were prepared by lysing the cells with RIPA (Boston BioProducts). Twenty-three μg of protein was loaded in a SDS-PAGE gel and identified using SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH (Sigma). Li-Cor donkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit 800CW were used as secondary antibodies and detected by Odyssey imager (Li-Cor). RNA was isolated from the cells and retrotranscribed using MagMax for Microarray and Superscript VILO II (Life Technologies), respectively, according to the manufacturer manual, and then analyzed with the NanoString® assay.


Expression of SF3B1K700E and SF3B1Q699H/K700E induced aberrant splicing, whereas SF3B1Q699H alone or SF3B1A745V or SF3B1R1074H (a substitution conferring resistance to the spliceosome inhibitor pladienolide B) did not induce aberrant splicing (FIG. 6), indicating that SF3B1Q999H is a non-functional substitution.


These data confirm that Panc 05.04 and Nalm-6 SF3B1K700E isogenic cells are representative models to study the functional activity of SF3B1 neomorphic mutations and the activity of splicing inhibitors in vitro and in vivo.


Example 3: Neomorphic SF3B1 Mutations Induce Abnormal mRNA Splicing

The functional activity of neomorphic mutations found in SF3B1MUT cancers was analyzed by expressing SF3B1WT, neomorphic SF3B1 mutants, or SF3B1K700R (the mutation observed in a renal clear cell carcinoma patient that clusters with SF3B1WT patients) in 293FT cells and determining splicing aberrations by NanoString®. The expression of all constructs was confirmed by western blot (FIG. 7). All SF3B1 neomorphic mutations tested demonstrated the same usage of alternative splice sites observed in patient samples (“MUT isoform” in FIG. 8), but SF3B1K700R and SF3B1WT did not show aberrant splicing (FIG. 8). Moreover, the expression of none of the SF3B1 constructs changed the overall gene expression (“PAN-gene” in FIG. 8) or the canonical splice isoforms (“WT isoform” in FIG. 8). This indicated both a correlation between the presence of the neomorphic SF3B1 mutations and alternative splicing as well as similar functional activity of the different neomorphic mutations, as was indicated by the RNA-Seq analysis of patient samples.


The correlation between the SF3B1K700E neomorphic mutation and aberrant splicing was analyzed using tetracycline-inducible shRNA to selectively knockdown the neomorphic SF3B1 mutant or SF3B1WT allele in Panc 05.04 and Panc 10.05 cell lines (neomorphic SF3B1MUT and SF3B1WT cell lines, respectively; obtained from the American Type Culture Collection [ATCC] or from RIKEN BioResource Center and cultured as instructed).


For the knockdown experiment, virus encoding shRNA was prepared in LentiX-293T cells (Clontech), which were cultured according to the manufacturer's instruction. The inducible shRNA were cloned into AgeI and EcoRI of the pLKO-iKD-H1 puro vector. The sequences of hairpins were:











shRNA #13 SF3B1PAN



(SEQ ID NO: 1180)



GCGAGACACACTGGTATTAAG,







shRNA #8 SF3B1WT



(SEQ ID NO: 1181)



TGTGGATGAGCAGCAGAAAGT;



and







shRNA #96 SF3B1MUT



(SEQ ID NO: 1182)



GATGAGCAGCATGAAGTTCGG.






Cells were transfected with 2.4 μg of target pLKO-shRNA plasmid, plus 2.4 μg of p Δ8.91 (packaging), and 0.6 μg VSVG (envelope) using TransIT reagent (Mirus). The virus was used to infect Panc 05.04 and Panc 10.05 by spin infection using Polybrene (Millipore). The day after infection, the cells were cultured in selecting media (1.25 μg/ml Puromycin [Life Technologies]) for 7 days to select for shRNA-expressing cells. The selected cells were cultured in the presence or absence of Doxycycline hyclate (100 ng/mL; Sigma) to induce the shRNA. Cells were harvested for protein and RNA at day 4 post-induction. In addition, cells were seeded for colony forming assay and CellTiter-Glo® assay (Promega). At day 9, cells were fixed with formaldehyde and stained with crystal violet.


To confirm SF3B1 knockdown using western blots, protein extracts were prepared by lysing the cells with RIPA (Boston BioProducts). Twenty to 25 μg of protein from each sample was separated by SDS-PAGE and transferred to nitrocellulose membranes (iblot, Life Technologies). Membranes were first blocked with Odyssey Blocking Buffer (Li-Cor) and then incubated with SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH (Sigma). Li-Cor donkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit 800CW were used as secondary antibodies and detected by Odyssey imager (Li-Cor).


To confirm SF3B1 knockdown by allele specific qPCR, RNA was isolated from the cells and retrotranscribed using MagMax for Microarray and Superscript VILO II (Life Technologies), respectively according to the manufacturer manual. qPCR was performed using ViiA7 (Life Technologies). The reaction included 20-50 ng cDNA, Power SYBR green master mix (Life Technologies) and 300 nM primers. The following primers were used:











SF3B1WT: FW



(SEQ ID NO: 1183)



5′-GACTTCCTTCTTTATTGCCCTTC



and







RW



(SEQ ID NO: 1184)



5′-AGCACTGATGGTCCGAACTTTC,







SF3B1MUT: FW



(SEQ ID NO: 1185)



5′-GTGTGCAAAAGCAAGAAGTCC



and







RW



(SEQ ID NO: 1186)



5′-GCACTGATGGTCCGAACTTCA,







SF3B1PAN: FW



(SEQ ID NO: 1187)



5′-GCTTGGCGGTGGGAAAGAGAAATTG



and







RW



(SEQ ID NO: 1188)



5′-AACCAGTCATACCACCCAAAGGTGTTG,







β-actin (internal control): FW



(SEQ ID NO: 1189)



5′-GGCACCCAGCACAATGAAGATCAAG



and







RW



(SEQ ID NO: 1190)



5′-ACTCGTCATACTCCTGCTTGCTGATC.







Biological and technical triplicates were performed.


The western blotting and allele specific PCR both confirmed knockdown of the SF3B1 alleles (FIGS. 9 and 10).


To determine the association between the expression of SF3B1 mutations and aberrant splicing, RNA isolated from the cells following doxycycline-induced knockdown was analyzed by NanoString®. In Panc 05.04, after knockdown of the neomorphic SF3B1MUT allele, the aberrant splice variants were downregulated and the canonical splice variants were upregulated, whereas the opposite was observed with selective depletion of the SF3B1WT allele (FIG. 11A), indicating that the neomorphic SF3B1MUT protein does not possess wild-type splicing activity. The expression of a pan shRNA induced the regulation of all splice variants as well as the depletion of SF3B1WT in Panc 10.05 cells (FIG. 11B). SF3B1PAN knockdown impaired growth and colony formation in both cell lines, while a minimal effect was observed with selective depletion of neomorphic SF3B1MUT in Panc05.04 cells (FIGS. 12 and 13). When the SF3B1WT allele was knocked down in Panc 05.04 cells, only a partial viability effect was observed, whereas SF3B1PAN knockdown prevented colony formation and cell proliferation (FIGS. 12 and 14), indicating that pan-inhibition of SF3B1 leads to antitumor activity in vitro and in vivo.


Example 4: Modulation of Neomorphic SF3B1MUT Splicing

Overall Effect of E7107 on Splicing


E7107 is a small-molecule compound that inhibits splicing by targeting the U2 snRNP-associated complex SF3B (Kotake, Y. et al. “Splicing factor SF3b as a target of the antitumor natural product pladienolide.” Nat Chem Biol 3, 570-575, doi:10.1038/nchembio.2007.16 [2007]). The ability of E7107 to inhibit splicing was observed in an in vitro splicing assay (IVS) using the substrate Ad2 (Pellizzoni, L., Kataoka, N., Charroux, B. & Dreyfuss, G. “A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.” Cell 95, 615-624 [1998]) and nuclear extracts from the Nalm-6 isogenic cell lines or 293F cells (Life Technologies; cultured according to the manufacturer's instructions) expressing Flag-tag SF3B1WT or SF3B1K700E, as follows.


Nuclear extracts were prepared from 293F cells transfected with pFLAG-CMV-2-SF3B1 plasmids, or from isogenic Nalm-6 cells (SBH Sciences). The plasmids were generated by cloning the mxSF3B1 gene into the HindIII and KpnI sites of pFLAG-CMV2 (Sigma), and the mutations mxSF3B1K700E, mxsF3B1R1074H and mxSF3B1K700E-R1074H were introduced using the same site-directed mutagenesis kit. Cell pellets were resuspended in hypotonic buffer (10 mM HEPES pH 7.9, 1.5 mM MgCl2, 10 mM KCl, 0.2 mM PMSF, and 0.5 mM DTT; for Nalm-6 cells, 40 mM KCl was used). The suspension was brought up to a total of five packed cell volumes (PCV). After centrifugation, the supernatant was discarded, and the cells were brought up to 3 PCV with hypotonic buffer, and incubated on ice for 10 minutes. Cells were lysed using a dounce homogenizer and then centrifuged. The supernatant was discarded, and the pellet was resuspended with ½ packed nuclear volume (PNV) of low salt buffer (20 mM HEPES pH 7.9, 1.5 mM MgCl2, 20 mM KCl, 0.2 mM EDTA, 25% glycerol, 0.2 mM PMSF, 0.5 mM DTT), followed by ½ PNV of high salt buffer (same as low salt buffer except 1.4M KCl was used). The nuclei were gently mixed for 30 minutes before centrifuging. The supernatant (nuclear extract) was then dialyzed into storage buffer (20 mM HEPES pH 7.9, 100 mM KCl, 0.2 mM EDTA, 20% glycerol, 0.2 mM PMSF, 0.5 mM DTT). Protein concentration was determined using NanoDrop 8000 UV-Vis spectrophotometer (Thermo Scientific).


For in vitro splicing (IVS) reactions, an Ad2-derived sequence (Pellizzoni, L., Kataoka, N., Charroux, B. & Dreyfuss, G. “A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.” Cell 95, 615-624 [1998]) was cloned into the pGEM-3Z vector (Promega) using EcoRI and XbaI restriction sites. The resulting pGEM-3Z-Ad2 plasmid was linearized using XbaI, purified, resuspended in TE buffer, and used as a DNA template in the in vitro transcription reaction. The Ad2 pre-mRNA was generated and purified using MEGAScript T7 and MegaClear kits, respectively (Invitrogen). Twenty μL splicing reactions were prepared using 80 μg nuclear extracts, 20 U RNAsin Ribonuclease inhibitor (Promega), 10 ng Ad2 pre-mRNA, and varying concentrations of E7107. After a 15 minute pre-incubation, activation buffer (0.5 mM ATP, 20 mM creatine phosphate, 1.6 mM MgCl2) was added to initiate splicing, and the reactions were incubated for 90 minutes. RNA was extracted using a modified protocol from a RNeasy 96 Kit (Qiagen). The splicing reactions were quenched in 350 μL Buffer RLT Plus (Qiagen), and 1.5 volume ethanol was added. The mixture was transferred to an RNeasy 96 plate, and the samples were processed as described in the kit protocol. RNA was diluted 1/10 with dH2O. 10 μL RT-qPCR reactions were prepared using TaqMan RNA-to-CT 1-step kit (Life Technologies), 8.5 μL RNA, and 1 μL of Ad2 mRNA primers/probe set (FW 5′ ACTCTCTTCCGCATCGCTGT (SEQ ID NO: 1191), RW 5′-CCGACGGGTTTCCGATCCAA (SEQ ID NO: 1192) and probe 5′ CTGTTGGGCTCGCGGTTG (SEQ ID NO: 1193)).


To evaluate pSF3B1, in vitro splicing reactions were prepared as described above. To quench the reactions, 6× Laemmli Buffer (Boston Bioproducts) was added, and the samples were subjected to SDS-PAGE gels (Life Technologies). The separated proteins were transferred onto nitrocellulose membranes then blocked with blocking buffer (50% Odyssey Blocking Buffer (Li-Cor Biosciences) and 50% TBST). The blots were incubated with anti-SF3B1 antibody overnight, after several washes in TBST, they were incubated with IRDye 680LT donkey-a-mouse-IgG antibody and visualized using an Odyssey CLx imaging system (Li-Cor Biosciences).


E7107 was able to inhibit splicing in nuclear extracts from both the Nalm-6 cells or the 293F cells expressing Flag-tag SF3B1WT or SF3B1K700E (FIGS. 15A and 15B).


E7107 Binds Both SF3B1WT and SF3B1K700E Proteins


The ability of E7107 to bind both SF3B1WT and SF3B1K700E proteins was evaluated in a competitive binding assay using Flag-tag SF3B1 proteins immunoprecipitated with anti-Flag antibody from transiently transfected 293F cells. Batch immobilization of antibody to beads was prepared by incubating 80 μg of anti-SF3B1 antibody (MBL International) and 24 mg anti-mouse PVT SPA scintillation beads (PerkinElmer) for 30 minutes. After centrifugation, the antibody-bead mixture was resuspended in PBS supplemented with PhosSTOP phosphatase inhibitor cocktail (Roche) and complete ULTRA protease inhibitor cocktail (Roche). Nuclear extracts were prepared by diluting 40 mg into a total volume of 16 mL PBS with phosphatase and protease inhibitors, and the mixture was centrifuged. The supernatant was transferred into a clean tube, and the antibody-bead mixture was added and incubated for two hours. The beads were collected by centrifuging, washed twice with PBS+0.1% Triton X-100, and resuspended with 4.8 mL of PBS. 100 μL binding reactions were prepared using slurry and varying concentrations of E7107. After 15 minutes pre-incubation at room temperature, one nM 3H-probe molecule (described in Kotake, Y. et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol 3, 570-575, doi:10.1038/nchembio.2007.16 [2007]) was added. The mixture was incubated at room temperature for 15 minutes, and luminescence signals were read using a MicroBeta2 Plate Counter (PerkinElmer).


As shown in FIG. 16A, E7107 was able to competitively inhibit binding of the 3H-probe molecule in a similar manner to either SF3B1WT (IC50: 13 nM) or SF3B1K700E (IC50: 11 nM).


Effect of E7107 and Other Compounds on Normal and Aberrant Splicing


E7107 was also tested in vitro in Nalm-6 isogenic cell lines for the ability to modulate normal and aberrant splicing induced by SF3B1WT and SF3B1K700E protein. Nalm-6 isogenic cells were treated with increasing concentrations of E7107 for six hours and RNA was analyzed by qPCR. As shown in FIG. 16B, canonical splicing was observed, with accumulation of pre-mRNA for EIF4A1 and downregulation of the mature mRNA SLC25A19 observed in both cell lines. Additionally, downregulation of mature mRNA of the two abnormally spliced isoforms of COASY and ZDHHC16 was observed in Nalm-6 SF3B1K700E (FIG. 16B).


To investigate the broader activity of E7107 on normal and aberrant splicing, RNA from Nalm-6 isogenic cells treated for two and six hours at 15 nM was analyzed by NanoString®. Only partial inhibition of splicing was observed at two hours in both isogenic cell lines, and at the level of gene, WT-associated isoforms, and MUT-associated isoform expression. After six hours of treatment, clear inhibition was detected for all isoforms quantified (FIG. 17). Similar results were obtained by RNA-Seq analysis of isogenic cell lines treated for six hours with E7107 at 15 nM (FIG. 18). Normal and aberrant splicing in the isogenic cell lines was also analyzed by RNA-Seq following treatment with one of additional compounds having formulas 1 or 2. Like E7107, each of these additional compounds inhibited expression of both WT-associated and MUT-associated RNA isoforms (FIG. 19; compound is indicated by formula number above each vertical pair of graphs). For the RNA-Seq analysis, cells were washed with PBS after treatment with E7107 or other test compound, and RNA was isolated using PureLink (Life Technology) as reported in the manufacturer's manual. cDNA library preparation, sequencing and raw read filtering was performed as described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012).


In addition, the ability of E7107 to modulate splicing was tested in mice bearing human tumor xenografts. Nalm-6 isogenic xenograft mice were generated by subcutaneously implanting 10×106 Nalm-6 isogenic cells into the flank of CB17-SCID mice, and tumors from these mice were collected at different timepoints after a single intravenous (IV) dose of E7107 (5 mg/kg) and analyzed to determine compound concentrations and splicing regulation. RNA was isolated from the tumors using RiboPure™ RNA purification kit (Ambion®) and used for NanoString® assay or qPCR. The RNA was retrotranscribed according to the instructions of the SuperScript® VILO™ cDNA synthesis kit (Invitrogen™) and 0.04 μl of cDNA was used for qPCR. qPCR for pre-mRNA EIF4A1 and mature mRNA SLC24A19 and pharmacokinetic evaluation were performed as described in Eskens, F. A. et al. “Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors.” Clin Cancer Res 19, 6296-6304, doi:10.1158/1078-0432.CCR-13-0485 (2013). The primers and probes used for ZDHHC16 were the following: FW 5′-TCTTGTCTACCTCTGGTTCCT (SEQ ID NO: 1194), RW 5′ CCTTCTTGTTGATGTGCCTTTC (SEQ ID NO: 1195) and probe 5′ FAM CAGTCTTCGCCCCTCTTTTCTTAG (SEQ ID NO: 1196). The primers and probes used for COASY were the following: FW 5′-CGGTGGTGCAAGTGGAA (SEQ ID NO: 1197), RW 5′-GCCTTGGTGTCCTCATTTCT (SEQ ID NO: 1198) and probe 5′-FAM-CTTGAGGTTTCATTTCCCCCTCCC (SEQ ID NO: 1199). E7107 reached similar drug concentrations and modulated canonical splicing (accumulation of pre-mRNA for EIF4A1 and downregulation of the mature mRNA SLC25A19) in both Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E models and downregulated abnormal splicing of COASY and ZDHHC16 in the Nalm-6 SF3B1K700E cells (FIG. 20), as observed in vitro. The canonical and aberrant splice mRNA isoforms were downregulated by E7107 as early as one hour following administration of the compound, and expression normalized shortly after treatment (FIG. 21), consistent with E7107 pharmacokinetic profile. Similar results were observed in a Panc 05.04 neomorphic SF3B1 xenograft model (FIG. 22). All these data indicate that E7107 is a pan-splicing modulator that can bind and inhibit SF3B1WT and SF3B1K700E proteins in vitro and in vivo.


Example 5: E7107 has Anti-Tumor Activity Via SF3B1 Modulation

SF3B1 modulator E7107 was tested for antitumor activity in vivo by determining the effect of E7107 in a subcutaneous model of Nalm-6 SF3B1K700E. 10×106 Nalm-6 SF3B1K700E were subcutaneously implanted into the flank of CB17-SCID mice, and mice were administered E7107 intravenously once a day for 5 consecutive days (QD×5) at three well tolerated dose levels (1.25, 2.5 and 5 mg/kg). After this dosing, the animals were monitored until they reached either of the following endpoints: 1) excessive tumor volume measured three times a week (tumor volume calculated by using the ellipsoid formula: (length×width)/2), or 2) development of any health problem such as paralysis or excessive body weight loss. Partial regression (PR) and complete regression (CR) are defined as 3 consecutive tumor measurements <50% and <30% of starting volume respectively.


In the 1.25 mg/kg group, all animals (n=10) reached complete regression (CR) in the Nalm-6 SF3B1K700E xenograft group. In the 2.5 mg/kg group, 10/10 CRs were observed in the Nalm-6 SF3B1K700E group by day 9. In the 5 mg/kg group all Nalm-6 SF3B1K700E xenograft animals reached CR as early as 9 days post treatment and had mean survival times of over 250 days (FIGS. 23 and 24). These data demonstrate antitumor activity of SF3B1 modulator in SF3B1K700E xenografts in vivo.


The ability of E7107 to inhibit splicing in CLL patient samples in vitro was determined by isolating RNA from samples of E7107-treated patient cells treated for 6 hours with E7107 at 10 nM and performing RNA-Seq analysis. To do so, cells were washed with PBS after treatment with E7107, and RNA was isolated using PureLink (Life Technology) as reported in the manufacturer's manual. cDNA library preparation, sequencing and raw read filtering was performed as described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012). As shown in FIG. 25, E7107 inhibited the expression of canonical splice isoforms in SF3B1WT and neomorphic SF3B1MUT patient samples. E7107 was able to modulate aberrant splicing in all CLL patient samples carrying neomorphic SF3B1 mutations.


Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims
  • 1-20. (canceled)
  • 21. A method of treating a patient having a neoplastic disorder, comprising administering an SF3B1-modulating compound to the patient, wherein a sample from the patient has been tested to determine expression levels of aberrant and canonical splice variants of TMEM14C, and the sample expresses an elevated ratio of aberrant to canonical splice variants of TMEM14C relative to the ratio in a control sample.
  • 22. The method of claim 21, wherein one or more aberrant splice variants comprise SEQ ID NO:95.
  • 23. The method of claim 21, wherein one or more canonical splice variants comprise SEQ ID NO:96.
  • 24. The method of claim 21, wherein the sample comprises a blood sample, a bone marrow aspirate, and/or a bone marrow biopsy.
  • 25. The method of claim 21, wherein the sample from the patient treated with the SF3B1-modulating compound further comprises a neomorphic SF3B1 mutation.
  • 26. The method of claim 25, wherein the neomorphic SF3B1 mutation comprises a mutation at one or more of positions selected from E622, H662, R625, K666, K700, and V701 in SF3B1.
  • 27. The method of claim 25, wherein the neomorphic SF3B1 mutation comprises a mutation at one or more of positions selected from H662, R625, and K700 in SF3B1.
  • 28. The method of claim 25, wherein the neomorphic SF3B1 mutation comprises R625C and/or K700E.
  • 29. The method of claim 25, wherein the control sample expresses a wild type or non-neomorphic SF3B1 protein.
  • 30. The method of claim 21, wherein the neoplastic disorder is a myeloid neoplasm.
  • 31. The method of claim 30, wherein the myeloid neoplasm is myelodysplastic syndrome, acute myeloid leukemia, or chronic myelomonocytic leukemia.
  • 32. The method of claim 21, wherein the neoplastic disorder is myelodysplastic syndrome.
  • 33. The method of claim 21, wherein the SF3B1-modulating compound comprises a compound of formula 2:
  • 34. A method of treating a patient having a neoplastic disorder, comprising: a) identifying an elevated ratio of aberrant to canonical splice variants of TMEM14C in a sample from the patient relative to the ratio in a control sample; andb) administering an SF3B1-modulating compound to the patient.
  • 35. The method of claim 34, wherein one or more aberrant splice variants comprise SEQ ID NO:95.
  • 36. The method of claim 34, wherein one or more canonical splice variants comprise SEQ ID NO:96.
  • 37. The method of claim 34, wherein identifying an elevated ratio comprises nucleic acid barcoding, real-time polymerase chain reaction (RT-PCR), microarray, nucleic acid sequencing, nanoparticle probes, and/or in situ hybridization.
  • 38. The method of claim 34, wherein identifying an elevated ratio comprises nucleic acid barcoding.
  • 39. The method of claim 34, wherein identifying an elevated ratio comprises RT-PCR.
  • 40. The method of claim 34, wherein the sample comprises a blood sample, a bone marrow aspirate, and/or a bone marrow biopsy.
  • 41. The method of claim 34, wherein the sample from the patient treated with the SF3B1-modulating compound further comprises a neomorphic SF3B1 mutation.
  • 42. The method of claim 41, wherein the neomorphic SF3B1 mutation comprises a mutation at one or more of positions selected from E622, H662, R625, K666, K700, and V701 in SF3B1.
  • 43. The method of claim 41, wherein the neomorphic SF3B1 mutation comprises a mutation at one or more of positions selected from H662, R625, and K700 in SF3B1.
  • 44. The method of claim 41, wherein the neomorphic SF3B1 mutation comprises R625C and/or K700E.
  • 45. The method of claim 41, wherein the control sample expresses a wild type or non-neomorphic SF3B1 protein.
  • 46. The method of claim 34, wherein the neoplastic disorder is a myeloid neoplasm.
  • 47. The method of claim 46, wherein the myeloid neoplasm is myelodysplastic syndrome, acute myeloid leukemia, or chronic myelomonocytic leukemia.
  • 48. The method of claim 34, wherein the neoplastic disorder is myelodysplastic syndrome.
  • 49. The method of claim 34, wherein the SF3B1-modulating compound comprises a compound of formula 2:
Parent Case Info

The present application is a continuation of U.S. patent application Ser. No. 15/755,225, filed Feb. 26, 2018, which is a national stage application under 35 U.S.C. § 371 of international application number PCT/US2016/049490, filed Aug. 30, 2016, which designated the U.S. and claims the benefit of priority to U.S. Provisional Patent Application No. 62/212,876, filed Sep. 1, 2015, the contents of which are hereby incorporated by reference herein in their entirety.

Provisional Applications (1)
Number Date Country
62212876 Sep 2015 US
Continuations (1)
Number Date Country
Parent 15755225 Feb 2018 US
Child 17098940 US