rs3816668

Positions:

chr8-11549084-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001715.3(BLK):c.330T>C(p.Ser110Ser) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.386

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
BLK	NM_001715.3 link	c.330T>C	p.Ser110Ser	synonymous_variant	5/13	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BLK	ENST00000259089.9 link	c.330T>C	p.Ser110Ser	synonymous_variant	5/13	1	NM_001715.3	ENSP00000259089.4	P51451
BLK	ENST00000533828.1 link	n.528T>C		non_coding_transcript_exon_variant	3/3	4
BLK	ENST00000645242.1 link	n.481T>C		non_coding_transcript_exon_variant	4/12
BLK	ENST00000696154.2 link	n.481T>C		non_coding_transcript_exon_variant	4/12				A0A8Q3SIE3

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73752

AN:

151890

Hom.:

18672

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.488

AC XY:

353435

AN XY:

724500

show subpopulations

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.:

AF XY:

0.478

AC XY:

35494

AN XY:

74296

show subpopulations

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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. -

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over