8-11540674-A-G

Variant names:

• chr8-11540674-A-G
• rs9657551
• NM_001715.3:c.-1-2550A>G

Variant summary

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

The NM_001715.3(BLK):​c.-1-2550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,894 control chromosomes in the GnomAD database, including 11,294 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 0.37 (11294 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-2550A>G		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.-1-2550A>G		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-5378A>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-5378A>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56105 AN: 151776 Hom.: 11269 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.370 AC: 56166 AN: 151894 Hom.: 11294 Cov.: 32 AF XY: 0.378 AC XY: 28088 AN XY: 74238

African (AFR) AF: 0.310 AC: 12840 AN: 41432

American (AMR) AF: 0.537 AC: 8200 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3888 AN: 5164

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4820

European-Finnish (FIN) AF: 0.384 AC: 4032 AN: 10508

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22925 AN: 67932

Other (OTH) AF: 0.383 AC: 806 AN: 2102

Alfa AF: 0.328 Hom.: 1348

Bravo AF: 0.385

Asia WGS AF: 0.610 AC: 2115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		-1.1
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: rs9657551; hg19: chr8-11398183;