rs4840568

Variant names:

• chr8-11493510-G-A
• rs4840568
• ENST00000645242.1:n.274+6343G>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+6343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,920 control chromosomes in the GnomAD database, including 9,059 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 0.33 (9059 hom., cov: 32)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 35 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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+6343G>A		intron	N/A
	BLK	ENST00000696154.2		n.274+6343G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49662 AN: 151802 Hom.: 9032 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.327 AC: 49739 AN: 151920 Hom.: 9059 Cov.: 32 AF XY: 0.332 AC XY: 24683 AN XY: 74242

African (AFR) AF: 0.342 AC: 14148 AN: 41424

American (AMR) AF: 0.482 AC: 7363 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 678 AN: 3466

East Asian (EAS) AF: 0.705 AC: 3640 AN: 5160

South Asian (SAS) AF: 0.366 AC: 1758 AN: 4808

European-Finnish (FIN) AF: 0.275 AC: 2902 AN: 10560

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18309 AN: 67934

Other (OTH) AF: 0.326 AC: 686 AN: 2106

Alfa AF: 0.294 Hom.: 9676

Bravo AF: 0.349

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.41

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: rs4840568;

hg19: chr8-11351019;