rs13277113

Variant names:

• chr8-11491677-G-A
• rs13277113
• ENST00000645242.1:n.274+4510G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-11491677-G-A
• chr8-11491677-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645242.1(BLK):​n.274+4510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,694 control chromosomes in the GnomAD database, including 6,383 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 0.26 (6383 hom., cov: 33)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 166 publications found

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]

BLK Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young type 11

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 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+4510G>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+4510G>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39115 AN: 151576 Hom.: 6363 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.258 AC: 39153 AN: 151694 Hom.: 6383 Cov.: 33 AF XY: 0.266 AC XY: 19705 AN XY: 74162

African (AFR) AF: 0.139 AC: 5725 AN: 41106

American (AMR) AF: 0.445 AC: 6791 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3644 AN: 5176

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10552

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17180 AN: 67988

Other (OTH) AF: 0.265 AC: 557 AN: 2104

Alfa AF: 0.263 Hom.: 28592

Bravo AF: 0.272

Asia WGS AF: 0.523 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.075

Splicing

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

Other links and lift over

dbSNP: rs13277113; hg19: chr8-11349186; COSMIC: COSV52052926; COSMIC: COSV52052926;