rs2248932

Positions:

• chr8-11534141-A-G

Variant summary

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

The NM_001715.3(BLK):​c.-1-9083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,108 control chromosomes in the GnomAD database, including 27,267 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 0.59 (27267 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

Genes affected

BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-9083A>G		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-1-9083A>G		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000645242.1	n.275-11911A>G		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-11911A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89742 AN: 151990 Hom.: 27252 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.590 AC: 89781 AN: 152108 Hom.: 27267 Cov.: 33 AF XY: 0.583 AC XY: 43340 AN XY: 74354

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.584

Alfa AF: 0.633 Hom.: 61607

Bravo AF: 0.571

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.78

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: rs2248932; hg19: chr8-11391650;