9-130854062-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

The NM_005157.6(ABL1):​c.80-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,602,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

ABL1
NM_005157.6 splice_acceptor

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.32
Variant links:
Genes affected
ABL1 (HGNC:76): (ABL proto-oncogene 1, non-receptor tyrosine kinase) This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.050987326 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.5, offset of 3, new splice context is: ccccctttctcttccggaAGccc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
BP6
Variant 9-130854062-A-G is Benign according to our data. Variant chr9-130854062-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2415365.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABL1NM_005157.6 linkuse as main transcriptc.80-2A>G splice_acceptor_variant ENST00000318560.6 NP_005148.2
ABL1NM_007313.3 linkuse as main transcriptc.137-2A>G splice_acceptor_variant NP_009297.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABL1ENST00000318560.6 linkuse as main transcriptc.80-2A>G splice_acceptor_variant 1 NM_005157.6 ENSP00000323315 P00519-1
ABL1ENST00000372348.9 linkuse as main transcriptc.137-2A>G splice_acceptor_variant 1 ENSP00000361423 P1P00519-2
ABL1ENST00000393293.4 linkuse as main transcriptc.137-5A>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 ENSP00000376971

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000290
AC:
7
AN:
241714
Hom.:
0
AF XY:
0.0000153
AC XY:
2
AN XY:
130520
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000217
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000828
AC:
12
AN:
1450130
Hom.:
0
Cov.:
30
AF XY:
0.00000555
AC XY:
4
AN XY:
720366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 02, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
D;D
GERP RS
5.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.33
Position offset: 13
DS_AL_spliceai
0.99
Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs767291130; hg19: chr9-133729449; API