NM_001715.3:c.-1-3877A>C

Variant names:

• chr8-11539347-A-C
• rs2409784
• NM_001715.3:c.-1-3877A>C

Variant summary

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

The NM_001715.3(BLK):​c.-1-3877A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,972 control chromosomes in the GnomAD database, including 21,505 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 0.52 (21505 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 23 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-3877A>C		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.-1-3877A>C		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-6705A>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-6705A>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78368 AN: 151856 Hom.: 21475 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.516 AC: 78431 AN: 151972 Hom.: 21505 Cov.: 32 AF XY: 0.532 AC XY: 39561 AN XY: 74298

African (AFR) AF: 0.418 AC: 17304 AN: 41412

American (AMR) AF: 0.650 AC: 9934 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3466

East Asian (EAS) AF: 0.994 AC: 5153 AN: 5184

South Asian (SAS) AF: 0.701 AC: 3375 AN: 4816

European-Finnish (FIN) AF: 0.627 AC: 6611 AN: 10552

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.483 AC: 32818 AN: 67950

Other (OTH) AF: 0.537 AC: 1130 AN: 2106

Alfa AF: 0.487 Hom.: 18545

Bravo AF: 0.519

Asia WGS AF: 0.806 AC: 2799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-0.68
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: rs2409784; hg19: chr8-11396856;