rs1382567

chr8-11493390-T-C

Variant summary

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

The ENST00000645242.1(BLK):n.274+6223T>C 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 0.409 in 152,100 control chromosomes in the GnomAD database, including 14,355 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 0.41 (14355 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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+6223T>C		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+6223T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62187 AN: 151982 Hom.: 14358 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.409 AC: 62187 AN: 152100 Hom.: 14355 Cov.: 32 AF XY: 0.398 AC XY: 29552 AN XY: 74342

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.00501

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.420

Alfa AF: 0.514 Hom.: 34011

Bravo AF: 0.393

Asia WGS AF: 0.174 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.3
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1382567; hg19: chr8-11350899; COSMIC: COSV52052187; COSMIC: COSV52052187;