rs13272061

Positions:

• chr8-11494752-G-T

Variant summary

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

The NM_001715.3(BLK):​c.-2+161G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,182 control chromosomes in the GnomAD database, including 13,048 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 0.37 (13048 hom., cov: 34)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+161G>T		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+161G>T		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000525389.1	n.423+161G>T		intron_variant, non_coding_transcript_variant		1
BLK	ENST00000645242.1	n.274+7585G>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+7585G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56433 AN: 152064 Hom.: 13052 Cov.: 34

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.371 AC: 56424 AN: 152182 Hom.: 13048 Cov.: 34 AF XY: 0.360 AC XY: 26818 AN XY: 74402

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.00501

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.394

Alfa AF: 0.431 Hom.: 2350

Bravo AF: 0.349

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13272061; hg19: chr8-11352261;