8-11556728-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001715.3(BLK):c.843T>C(p.Phe281Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,614,022 control chromosomes in the GnomAD database, including 569,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50797 hom., cov: 32)

Exomes 𝑓: 0.84 ( 519043 hom. )

Consequence

BLK
NM_001715.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

Publications

30 publications found

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 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

BLK links:

ENSG00000269954 (HGNC:58190):

ENSG00000269954 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 8-11556728-T-C is Benign according to our data. Variant chr8-11556728-T-C is described in ClinVar as Benign. ClinVar VariationId is 128529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.843T>C	p.Phe281Phe	synonymous_variant	Exon 9 of 13	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9 link	c.843T>C	p.Phe281Phe	synonymous_variant	Exon 9 of 13	1	NM_001715.3	ENSP00000259089.4

Frequencies

GnomAD3 genomes

AF:

0.814

AC:

123807

AN:

152030

Hom.:

50751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.895

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.778

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.832

GnomAD2 exomes

AF:

0.837

AC:

210438

AN:

251478

AF XY:

0.835

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.883

Gnomad EAS exome

AF:

0.951

Gnomad FIN exome

AF:

0.811

Gnomad NFE exome

AF:

0.842

Gnomad OTH exome

AF:

0.850

GnomAD4 exome

AF:

0.842

AC:

1230750

AN:

1461874

Hom.:

519043

Cov.:

AF XY:

0.840

AC XY:

611068

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.733

AC:

24528

AN:

33478

American (AMR)

AF:

0.865

AC:

38700

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

23036

AN:

26136

East Asian (EAS)

AF:

0.943

AC:

37424

AN:

39700

South Asian (SAS)

AF:

0.776

AC:

66896

AN:

86258

European-Finnish (FIN)

AF:

0.812

AC:

43359

AN:

53420

Middle Eastern (MID)

AF:

0.842

AC:

4854

AN:

5766

European-Non Finnish (NFE)

AF:

0.846

AC:

940738

AN:

1111996

Other (OTH)

AF:

0.848

AC:

51215

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12738

25476

38215

50953

63691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21136

42272

63408

84544

105680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.814

AC:

123908

AN:

152148

Hom.:

50797

Cov.:

AF XY:

0.813

AC XY:

60459

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.731

AC:

30332

AN:

41482

American (AMR)

AF:

0.859

AC:

13139

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3081

AN:

3472

East Asian (EAS)

AF:

0.949

AC:

4904

AN:

5168

South Asian (SAS)

AF:

0.778

AC:

3750

AN:

4818

European-Finnish (FIN)

AF:

0.804

AC:

8506

AN:

10582

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.844

AC:

57384

AN:

68012

Other (OTH)

AF:

0.835

AC:

1765

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1189

2377

3566

4754

5943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.833

Hom.:

48218

Bravo

AF:

0.816

Asia WGS

AF:

0.860

AC:

2989

AN:

3478

EpiCase

AF:

0.838

EpiControl

AF:

0.842

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Maturity-onset diabetes of the young type 11

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.1

(source)

DANN

Benign

0.68

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over