ENST00000645242.1:n.274+4285G>A

Variant names:

• chr8-11491452-G-A
• rs9693589
• ENST00000645242.1:n.274+4285G>A

Variant summary

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

The ENST00000645242.1(BLK):​n.274+4285G>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 151,924 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: 31)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000645242.1		n.274+4285G>A		intron	N/A
	BLK	ENST00000696154.2		n.274+4285G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39093 AN: 151806 Hom.: 6363 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.258 AC: 39129 AN: 151924 Hom.: 6383 Cov.: 31 AF XY: 0.265 AC XY: 19713 AN XY: 74260

African (AFR) AF: 0.138 AC: 5697 AN: 41428

American (AMR) AF: 0.444 AC: 6782 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.703 AC: 3633 AN: 5170

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4812

European-Finnish (FIN) AF: 0.273 AC: 2872 AN: 10530

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

European-Non Finnish (NFE) AF: 0.253 AC: 17164 AN: 67936

Other (OTH) AF: 0.266 AC: 561 AN: 2112

Alfa AF: 0.227 Hom.: 564

Bravo AF: 0.272

Asia WGS AF: 0.526 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs9693589; hg19: chr8-11348961;