8-11498312-A-G

Position:

• chr8-11498312-A-G

Variant summary

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

The NM_001715.3(BLK):​c.-2+3721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,082 control chromosomes in the GnomAD database, including 53,387 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 0.84 (53387 hom., cov: 31)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-2+3721A>G		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-2+3721A>G		intron_variant		1	NM_001715.3	P1
BLK	ENST00000525389.1	n.423+3721A>G		intron_variant, non_coding_transcript_variant		1
BLK	ENST00000645242.1	n.274+11145A>G		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+11145A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127025 AN: 151964 Hom.: 53333 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.836 AC: 127138 AN: 152082 Hom.: 53387 Cov.: 31 AF XY: 0.829 AC XY: 61603 AN XY: 74312

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.832

Alfa AF: 0.836 Hom.: 110298

Bravo AF: 0.852

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
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: rs2618479; hg19: chr8-11355821;