8-11502129-G-T

Variant names:

• chr8-11502129-G-T
• rs1600249
• NM_001715.3:c.-2+7538G>T

Variant summary

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

The NM_001715.3(BLK):​c.-2+7538G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,134 control chromosomes in the GnomAD database, including 5,963 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 0.24 (5963 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 40 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 (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+7538G>T		intron_variant	Intron 1 of 12	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-2+7538G>T		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000525389.1	n.424-7021G>T		intron_variant	Intron 1 of 1	1
BLK	ENST00000645242.1	n.274+14962G>T		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+14962G>T		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36002 AN: 152016 Hom.: 5945 Cov.: 33

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.237 AC: 36039 AN: 152134 Hom.: 5963 Cov.: 33 AF XY: 0.244 AC XY: 18150 AN XY: 74350

African (AFR) AF: 0.0820 AC: 3407 AN: 41542

American (AMR) AF: 0.452 AC: 6905 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3579 AN: 5178

South Asian (SAS) AF: 0.383 AC: 1847 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2385 AN: 10554

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16536 AN: 67986

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.258 Hom.: 17846

Bravo AF: 0.253

Asia WGS AF: 0.548 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1600249; hg19: chr8-11359638; COSMIC: COSV52052949;