ENST00000645242.1:n.274+6544A>C

Variant names:

• chr8-11493711-A-C
• rs1382568
• ENST00000645242.1:n.274+6544A>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+6544A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,852 control chromosomes in the GnomAD database, including 7,043 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 0.28 (7043 hom., cov: 31)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 19 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 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+6544A>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+6544A>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42014 AN: 151734 Hom.: 7018 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.277 AC: 42079 AN: 151852 Hom.: 7043 Cov.: 31 AF XY: 0.285 AC XY: 21136 AN XY: 74212

African (AFR) AF: 0.176 AC: 7296 AN: 41348

American (AMR) AF: 0.461 AC: 7043 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3667 AN: 5134

South Asian (SAS) AF: 0.361 AC: 1734 AN: 4802

European-Finnish (FIN) AF: 0.283 AC: 2979 AN: 10538

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17913 AN: 67958

Other (OTH) AF: 0.290 AC: 611 AN: 2108

Alfa AF: 0.717 Hom.: 14263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.32
DANN	Benign	0.73
PhyloP100		-0.096

Splicing

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

Other links and lift over

dbSNP: rs1382568; hg19: chr8-11351220;