rs76154097

Positions:

• chr8-11509533-C-T

Variant summary

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

The ENST00000259089.9(BLK):​c.-2+14942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,230 control chromosomes in the GnomAD database, including 1,101 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 0.10 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: BLK ENST00000259089.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+14942C>T		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-2+14942C>T		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000525389.1	n.807C>T		non_coding_transcript_exon_variant	2/2	1
BLK	ENST00000645242.1	n.274+22366C>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+22366C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15898 AN: 152100 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.104 AC: 15891 AN: 152218 Hom.: 1101 Cov.: 32 AF XY: 0.101 AC XY: 7535 AN XY: 74410

Gnomad4 AFR AF: 0.0293

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.0996

Alfa AF: 0.137 Hom.: 272

Bravo AF: 0.0941

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs76154097; hg19: chr8-11367042;