8-11498493-C-A

Variant names:

• chr8-11498493-C-A
• rs2618478
• NM_001715.3:c.-2+3902C>A

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+3902C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,240 control chromosomes in the GnomAD database, including 57,421 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 0.86 (57421 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+3902C>A		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+3902C>A		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000525389.1	n.423+3902C>A		intron_variant	Intron 1 of 1	1
BLK	ENST00000645242.1	n.274+11326C>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+11326C>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131535 AN: 152122 Hom.: 57359 Cov.: 33

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.865 AC: 131657 AN: 152240 Hom.: 57421 Cov.: 33 AF XY: 0.858 AC XY: 63822 AN XY: 74416

African (AFR) AF: 0.970 AC: 40308 AN: 41560

American (AMR) AF: 0.888 AC: 13593 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3472

East Asian (EAS) AF: 0.728 AC: 3768 AN: 5176

South Asian (SAS) AF: 0.818 AC: 3942 AN: 4818

European-Finnish (FIN) AF: 0.706 AC: 7472 AN: 10586

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56889 AN: 68010

Other (OTH) AF: 0.862 AC: 1822 AN: 2114

Alfa AF: 0.847 Hom.: 27679

Bravo AF: 0.882

Asia WGS AF: 0.819 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.31
PhyloP100		-0.11
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: rs2618478; hg19: chr8-11356002;