rs4841548

Positions:

• chr8-11517270-T-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+22679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,112 control chromosomes in the GnomAD database, including 5,532 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 0.25 (5532 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+22679T>C		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-2+22679T>C		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000645242.1	n.275-28782T>C		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-28782T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38531 AN: 151994 Hom.: 5528 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.253 AC: 38550 AN: 152112 Hom.: 5532 Cov.: 32 AF XY: 0.245 AC XY: 18200 AN XY: 74380

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.276

Alfa AF: 0.316 Hom.: 16579

Bravo AF: 0.253

Asia WGS AF: 0.0910 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
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: rs4841548; hg19: chr8-11374779;