rs13277113

chr8-11491677-G-Achr8-11491677-G-T

Variant summary

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

The ENST00000645242.1(BLK):n.274+4510G>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 0.258 in 151,694 control chromosomes in the GnomAD database, including 6,383 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 0.26 (6383 hom., cov: 33)
• Consequence: BLK ENST00000645242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 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+4510G>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+4510G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39115 AN: 151576 Hom.: 6363 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.258 AC: 39153 AN: 151694 Hom.: 6383 Cov.: 33 AF XY: 0.266 AC XY: 19705 AN XY: 74162

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.265

Alfa AF: 0.262 Hom.: 13702

Bravo AF: 0.272

Asia WGS AF: 0.523 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13277113; hg19: chr8-11349186; COSMIC: COSV52052926; COSMIC: COSV52052926;