rs4840568

Variant names:

• chr8-11493510-G-A
• rs4840568
• ENST00000645242.1:n.274+6343G>A

Variant summary

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

The ENST00000645242.1(BLK):​n.274+6343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,920 control chromosomes in the GnomAD database, including 9,059 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 0.33 (9059 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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 (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000645242.1	n.274+6343G>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+6343G>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49662 AN: 151802 Hom.: 9032 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.327 AC: 49739 AN: 151920 Hom.: 9059 Cov.: 32 AF XY: 0.332 AC XY: 24683 AN XY: 74242

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.326

Alfa AF: 0.284 Hom.: 1055

Bravo AF: 0.349

Asia WGS AF: 0.556 AC: 1932 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	1.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4840568; hg19: chr8-11351019;