9-130755834-T-C

Variant names:

• chr9-130755834-T-C
• rs2583836
• ENST00000372348.9:c.136+41379T>C

Variant summary

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

The ENST00000372348.9(ABL1):​c.136+41379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,072 control chromosomes in the GnomAD database, including 23,595 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 0.53 (23595 hom., cov: 32)
• Consequence: ABL1 ENST00000372348.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372348.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	NM_007313.3		c.136+41379T>C		intron	N/A	NP_009297.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	ENST00000372348.9	TSL:1	c.136+41379T>C		intron	N/A	ENSP00000361423.2
	ABL1	ENST00000393293.4	TSL:5	c.136+41379T>C		intron	N/A	ENSP00000376971.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81048 AN: 151954 Hom.: 23547 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.534 AC: 81156 AN: 152072 Hom.: 23595 Cov.: 32 AF XY: 0.534 AC XY: 39730 AN XY: 74336

African (AFR) AF: 0.767 AC: 31818 AN: 41472

American (AMR) AF: 0.557 AC: 8505 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1765 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3258 AN: 5166

South Asian (SAS) AF: 0.556 AC: 2679 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3897 AN: 10576

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27559 AN: 67988

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.448 Hom.: 7748

Bravo AF: 0.562

Asia WGS AF: 0.584 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.35
PhyloP100		0.91
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: rs2583836; hg19: chr9-133631221;