rs7026988

Variant names:

• chr9-130792512-C-T
• rs7026988
• ENST00000372348.9:c.137-61552C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372348.9(ABL1):​c.137-61552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,734 control chromosomes in the GnomAD database, including 4,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4859 hom., cov: 31)
• Consequence: ABL1 ENST00000372348.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 5 publications found

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]

ABL1 Gene-Disease associations (from GenCC):

• congenital heart defects and skeletal malformations syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• connective tissue disorder

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• bone development disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000309617 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_007313.3	c.137-61552C>T		intron_variant	Intron 1 of 10		NP_009297.2
LOC124902288	XR_007061823.1	n.247-9718G>A		intron_variant	Intron 2 of 2
LOC124902288	XR_007061824.1	n.247-4832G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000372348.9	c.137-61552C>T		intron_variant	Intron 1 of 10	1		ENSP00000361423.2
ABL1	ENST00000393293.4	c.137-61555C>T		intron_variant	Intron 1 of 1	5		ENSP00000376971.4
ENSG00000309617	ENST00000842460.1	n.243-9718G>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33121 AN: 151616 Hom.: 4855 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33156 AN: 151734 Hom.: 4859 Cov.: 31 AF XY: 0.215 AC XY: 15913 AN XY: 74156

African (AFR) AF: 0.428 AC: 17653 AN: 41260

American (AMR) AF: 0.200 AC: 3039 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3470

East Asian (EAS) AF: 0.0682 AC: 352 AN: 5162

South Asian (SAS) AF: 0.128 AC: 615 AN: 4800

European-Finnish (FIN) AF: 0.118 AC: 1243 AN: 10538

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9147 AN: 67972

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.163 Hom.: 8066

Bravo AF: 0.234

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7026988; hg19: chr9-133667899;