ENST00000645242.1:n.274+6002T>C

Variant names:

• chr8-11493169-T-C
• rs2736344
• ENST00000645242.1:n.274+6002T>C

Variant summary

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

The ENST00000645242.1(BLK):​n.274+6002T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,150 control chromosomes in the GnomAD database, including 52,605 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 0.83 (52605 hom., cov: 33)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 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+6002T>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+6002T>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126161 AN: 152032 Hom.: 52554 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.830 AC: 126269 AN: 152150 Hom.: 52605 Cov.: 33 AF XY: 0.822 AC XY: 61148 AN XY: 74354

African (AFR) AF: 0.858 AC: 35637 AN: 41512

American (AMR) AF: 0.868 AC: 13282 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2886 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3797 AN: 5172

South Asian (SAS) AF: 0.794 AC: 3823 AN: 4816

European-Finnish (FIN) AF: 0.692 AC: 7300 AN: 10548

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56936 AN: 68016

Other (OTH) AF: 0.825 AC: 1740 AN: 2108

Alfa AF: 0.848 Hom.: 21838

Bravo AF: 0.844

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs2736344; hg19: chr8-11350678;