8-11533270-A-T

Position:

• chr8-11533270-A-T

Variant summary

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

The NM_001715.3(BLK):​c.-1-9954A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,894 control chromosomes in the GnomAD database, including 25,689 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 0.57 (25689 hom., cov: 31)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-1-9954A>T		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-1-9954A>T		intron_variant		1	NM_001715.3	P1
BLK	ENST00000645242.1	n.275-12782A>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-12782A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86813 AN: 151776 Hom.: 25679 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.572 AC: 86841 AN: 151894 Hom.: 25689 Cov.: 31 AF XY: 0.565 AC XY: 41940 AN XY: 74206

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.571

Alfa AF: 0.538 Hom.: 1781

Bravo AF: 0.550

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2249040; hg19: chr8-11390779;