rs2251056

Positions:

• chr8-11492067-C-A

Variant summary

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

The ENST00000645242.1(BLK):​n.274+4900C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,016 control chromosomes in the GnomAD database, including 52,486 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 0.83 (52486 hom., cov: 30)
• Consequence: BLK ENST00000645242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000645242.1	n.274+4900C>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+4900C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125967 AN: 151898 Hom.: 52434 Cov.: 30

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.829 AC: 126076 AN: 152016 Hom.: 52486 Cov.: 30 AF XY: 0.822 AC XY: 61056 AN XY: 74292

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.825

Alfa AF: 0.846 Hom.: 21059

Bravo AF: 0.844

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2251056; hg19: chr8-11349576;