rs2855192

Positions:

• chr9-130852664-G-A
• chr9-130852664-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005157.6(ABL1):​c.80-1400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 151,822 control chromosomes in the GnomAD database, including 759 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 0.087 (759 hom., cov: 31)
• Consequence: ABL1 NM_005157.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABL1	NM_005157.6	c.80-1400G>A		intron_variant		ENST00000318560.6
ABL1	NM_007313.3	c.137-1400G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABL1	ENST00000318560.6	c.80-1400G>A		intron_variant		1	NM_005157.6
ABL1	ENST00000372348.9	c.137-1400G>A		intron_variant		1		P1
ABL1	ENST00000393293.4	c.137-1403G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13183 AN: 151704 Hom.: 759 Cov.: 31

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0868 AC: 13180 AN: 151822 Hom.: 759 Cov.: 31 AF XY: 0.0833 AC XY: 6178 AN XY: 74160

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0347

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0881 Hom.: 193

Bravo AF: 0.0880

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs2855192; hg19: chr9-133728051; COSMIC: COSV59323956;