rs76610494

chr8-11493006-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000645242.1(BLK):n.274+5839C>T 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 0.0126 in 152,248 control chromosomes in the GnomAD database, including 16 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 0.013 (16 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1922/152248) while in subpopulation AFR AF= 0.0207 (861/41540). AF 95% confidence interval is 0.0196. There are 16 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1921 AD gene.

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+5839C>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+5839C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1921 AN: 152130 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00911

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0126 AC: 1922 AN: 152248 Hom.: 16 Cov.: 32 AF XY: 0.0124 AC XY: 923 AN XY: 74454

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00913

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0125 Hom.: 2

Bravo AF: 0.0139

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.67
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76610494; hg19: chr8-11350515;