chr8-11527204-C-A

Variant names:

• chr8-11527204-C-A
• rs2252534
• NM_001715.3:c.-1-16020C>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.-1-16020C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,172 control chromosomes in the GnomAD database, including 54,816 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 0.84 (54816 hom., cov: 31)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-16020C>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.-1-16020C>A		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-18848C>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-18848C>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128253 AN: 152054 Hom.: 54763 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.844 AC: 128367 AN: 152172 Hom.: 54816 Cov.: 31 AF XY: 0.849 AC XY: 63139 AN XY: 74394

African (AFR) AF: 0.961 AC: 39933 AN: 41544

American (AMR) AF: 0.885 AC: 13540 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5044 AN: 5170

South Asian (SAS) AF: 0.851 AC: 4102 AN: 4822

European-Finnish (FIN) AF: 0.827 AC: 8749 AN: 10574

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51798 AN: 67988

Other (OTH) AF: 0.839 AC: 1771 AN: 2110

Alfa AF: 0.790 Hom.: 105403

Bravo AF: 0.857

Asia WGS AF: 0.915 AC: 3180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.60
DANN	Benign	0.18
PhyloP100		-0.15
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: rs2252534; hg19: chr8-11384713;