9-130790187-C-A

Variant names:

• chr9-130790187-C-A
• rs11244142
• ENST00000372348.9:c.137-63877C>A

Variant summary

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

The ENST00000372348.9(ABL1):​c.137-63877C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,158 control chromosomes in the GnomAD database, including 5,026 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 (5026 hom., cov: 33)
• Consequence: ABL1 ENST00000372348.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_007313.3	c.137-63877C>A		intron_variant	Intron 1 of 10		NP_009297.2
LOC124902288	XR_007061823.1	n.247-7393G>T		intron_variant	Intron 2 of 2
LOC124902288	XR_007061824.1	n.247-2507G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000372348.9	c.137-63877C>A		intron_variant	Intron 1 of 10	1		ENSP00000361423.2
ABL1	ENST00000393293.4	c.137-63880C>A		intron_variant	Intron 1 of 1	5		ENSP00000376971.4
ENSG00000309617	ENST00000842460.1	n.243-7393G>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33598 AN: 152040 Hom.: 5018 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.221 AC: 33649 AN: 152158 Hom.: 5026 Cov.: 33 AF XY: 0.217 AC XY: 16172 AN XY: 74396

African (AFR) AF: 0.436 AC: 18087 AN: 41456

American (AMR) AF: 0.201 AC: 3070 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3472

East Asian (EAS) AF: 0.0689 AC: 357 AN: 5182

South Asian (SAS) AF: 0.128 AC: 618 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1249 AN: 10596

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

European-Non Finnish (NFE) AF: 0.135 AC: 9154 AN: 68020

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.189 Hom.: 489

Bravo AF: 0.236

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.26
PhyloP100		-0.20
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: rs11244142; hg19: chr9-133665574;