8-11489780-T-G

Variant names:

• chr8-11489780-T-G
• rs2736342
• ENST00000645242.1:n.274+2613T>G

Variant summary

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

The ENST00000645242.1(BLK):​n.274+2613T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,964 control chromosomes in the GnomAD database, including 18,050 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 0.47 (18050 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645242.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000645242.1		n.274+2613T>G		intron	N/A
	BLK	ENST00000696154.2		n.274+2613T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71637 AN: 151846 Hom.: 18029 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.472 AC: 71707 AN: 151964 Hom.: 18050 Cov.: 32 AF XY: 0.458 AC XY: 34001 AN XY: 74306

African (AFR) AF: 0.478 AC: 19813 AN: 41424

American (AMR) AF: 0.353 AC: 5382 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2025 AN: 3472

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5184

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4130 AN: 10540

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37098 AN: 67950

Other (OTH) AF: 0.469 AC: 989 AN: 2108

Alfa AF: 0.436 Hom.: 2291

Bravo AF: 0.463

Asia WGS AF: 0.201 AC: 699 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.49
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs2736342; hg19: chr8-11347289;