8-11539948-C-G

Variant names:

• chr8-11539948-C-G
• rs2061830
• NM_001715.3:c.-1-3276C>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.-1-3276C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,016 control chromosomes in the GnomAD database, including 25,702 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 0.57 (25702 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-3276C>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.-1-3276C>G		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-6104C>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-6104C>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86611 AN: 151898 Hom.: 25652 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.570 AC: 86710 AN: 152016 Hom.: 25702 Cov.: 33 AF XY: 0.584 AC XY: 43398 AN XY: 74312

African (AFR) AF: 0.585 AC: 24260 AN: 41474

American (AMR) AF: 0.667 AC: 10198 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1396 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5165 AN: 5192

South Asian (SAS) AF: 0.705 AC: 3397 AN: 4818

European-Finnish (FIN) AF: 0.630 AC: 6642 AN: 10538

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33705 AN: 67922

Other (OTH) AF: 0.565 AC: 1195 AN: 2114

Alfa AF: 0.504 Hom.: 2363

Bravo AF: 0.579

Asia WGS AF: 0.830 AC: 2876 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.73
DANN	Benign	0.69
PhyloP100		-0.17
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: rs2061830; hg19: chr8-11397457;