8-11509528-G-C

Position:

• chr8-11509528-G-C

Variant summary

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

The NM_001715.3(BLK):​c.-2+14937G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,240 control chromosomes in the GnomAD database, including 777 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 0.092 (776 hom., cov: 32)
  • Exomes 𝑓: 0.077 (1 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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 (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-2+14937G>C		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-2+14937G>C		intron_variant		1	NM_001715.3	P1
BLK	ENST00000525389.1	n.802G>C		non_coding_transcript_exon_variant	2/2	1
BLK	ENST00000645242.1	n.274+22361G>C		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+22361G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13986 AN: 152096 Hom.: 775 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0673

GnomAD4 exome AF: 0.0769 AC: 2 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 2 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

GnomAD4 genome AF: 0.0918 AC: 13980 AN: 152214 Hom.: 776 Cov.: 32 AF XY: 0.0913 AC XY: 6798 AN XY: 74422

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0714

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0559 Hom.: 78

Bravo AF: 0.0867

Asia WGS AF: 0.0540 AC: 188 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	1.5
DANN	Benign	0.36

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: rs4629826; hg19: chr8-11367037;