rs7824640

Positions:

• chr8-11547548-G-A

Variant summary

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

The NM_001715.3(BLK):​c.176-484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,182 control chromosomes in the GnomAD database, including 15,986 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 0.45 (15986 hom., cov: 34)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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 = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.176-484G>A		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.176-484G>A		intron_variant		1	NM_001715.3	P1
BLK	ENST00000533828.1	n.374-484G>A		intron_variant, non_coding_transcript_variant		4
BLK	ENST00000645242.1	n.327-484G>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.327-484G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.447 AC: 68027 AN: 152064 Hom.: 15987 Cov.: 34

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.447 AC: 68055 AN: 152182 Hom.: 15986 Cov.: 34 AF XY: 0.440 AC XY: 32776 AN XY: 74410

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.0533

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.454

Alfa AF: 0.482 Hom.: 2210

Bravo AF: 0.436

Asia WGS AF: 0.262 AC: 916 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	5.3
DANN	Benign	0.86

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: rs7824640; hg19: chr8-11405057;