ENST00000645242.1:n.274+4900C>A

Variant names:

• chr8-11492067-C-A
• rs2251056
• ENST00000645242.1:n.274+4900C>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 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
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000645242.1	n.274+4900C>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+4900C>A		intron_variant	Intron 1 of 11

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;