rs2251056

Variant names:

• chr8-11492067-C-A
• rs2251056
• ENST00000645242.1:n.274+4900C>A

Variant summary

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

The ENST00000645242.1(BLK):​n.274+4900C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,016 control chromosomes in the GnomAD database, including 52,486 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 0.83 (52486 hom., cov: 30)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645242.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000645242.1		n.274+4900C>A		intron	N/A
	BLK	ENST00000696154.2		n.274+4900C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125967 AN: 151898 Hom.: 52434 Cov.: 30

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.829 AC: 126076 AN: 152016 Hom.: 52486 Cov.: 30 AF XY: 0.822 AC XY: 61056 AN XY: 74292

African (AFR) AF: 0.858 AC: 35566 AN: 41462

American (AMR) AF: 0.868 AC: 13271 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2886 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3764 AN: 5138

South Asian (SAS) AF: 0.789 AC: 3791 AN: 4802

European-Finnish (FIN) AF: 0.692 AC: 7305 AN: 10550

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56882 AN: 67984

Other (OTH) AF: 0.825 AC: 1743 AN: 2114

Alfa AF: 0.845 Hom.: 25429

Bravo AF: 0.844

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		0.012

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2251056;

hg19: chr8-11349576;