rs1382567

Variant names:

• chr8-11493390-T-C
• rs1382567
• ENST00000645242.1:n.274+6223T>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+6223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,100 control chromosomes in the GnomAD database, including 14,355 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 0.41 (14355 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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+6223T>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+6223T>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62187 AN: 151982 Hom.: 14358 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.409 AC: 62187 AN: 152100 Hom.: 14355 Cov.: 32 AF XY: 0.398 AC XY: 29552 AN XY: 74342

African (AFR) AF: 0.273 AC: 11313 AN: 41488

American (AMR) AF: 0.325 AC: 4974 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3468

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5192

South Asian (SAS) AF: 0.369 AC: 1778 AN: 4818

European-Finnish (FIN) AF: 0.391 AC: 4123 AN: 10554

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36637 AN: 67982

Other (OTH) AF: 0.420 AC: 886 AN: 2110

Alfa AF: 0.492 Hom.: 51563

Bravo AF: 0.393

Asia WGS AF: 0.174 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs1382567; hg19: chr8-11350899; COSMIC: COSV52052187; COSMIC: COSV52052187;