rs3816668

chr8-11549084-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001715.3(BLK):c.330T>C(p.Ser110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,609,686 control chromosomes in the GnomAD database, including 196,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18684 hom., cov: 32)
  • Exomes 𝑓: 0.49 (177742 hom.)
• Consequence: BLK NM_001715.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.386

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-11549084-T-C is Benign according to our data. Variant chr8-11549084-T-C is described in ClinVar as [Benign]. Clinvar id is 128527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11549084-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.386 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.330T>C	p.Ser110=	synonymous_variant	5/13	ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.330T>C	p.Ser110=	synonymous_variant	5/13	1	NM_001715.3	P1
BLK	ENST00000533828.1	n.528T>C		non_coding_transcript_exon_variant	3/3	4
BLK	ENST00000645242.1	n.481T>C		non_coding_transcript_exon_variant	4/12
BLK	ENST00000696154.2	n.481T>C		non_coding_transcript_exon_variant	4/12

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73752 AN: 151890 Hom.: 18672 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.493

GnomAD3 exomes AF: 0.443 AC: 107849 AN: 243242 Hom.: 26086 AF XY: 0.451 AC XY: 59265 AN XY: 131460

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.0708

Gnomad SAS exome AF: 0.465

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.486 AC: 708594 AN: 1457678 Hom.: 177742 Cov.: 56 AF XY: 0.488 AC XY: 353435 AN XY: 724500

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.0666

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.486 AC: 73806 AN: 152008 Hom.: 18684 Cov.: 32 AF XY: 0.478 AC XY: 35494 AN XY: 74296

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.488

Alfa AF: 0.516 Hom.: 33756

Bravo AF: 0.481

Asia WGS AF: 0.284 AC: 992 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Maturity-onset diabetes of the young type 11 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Systemic lupus erythematosus Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

BLK gene locus is associated with Systemic lupus erythematosus, sjogren's syndrome and other systemic inflammatory conditions. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs3816668; hg19: chr8-11406593; COSMIC: COSV52052315; COSMIC: COSV52052315;