8-11549084-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.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

Publications

26 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:

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=-0.65).

BP6

Variant 8-11549084-T-C is Benign according to our data. Variant chr8-11549084-T-C is described in ClinVar as Benign. ClinVar VariationId is 128527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Ensembl

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

GnomAD2 exomes

AF:

0.443

AC:

107849

AN:

243242

AF XY:

0.451

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 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

African (AFR)

AF:

0.525

AC:

17572

AN:

33440

American (AMR)

AF:

0.338

AC:

14912

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

16239

AN:

26062

East Asian (EAS)

AF:

0.0666

AC:

2643

AN:

39668

South Asian (SAS)

AF:

0.466

AC:

39660

AN:

85038

European-Finnish (FIN)

AF:

0.422

AC:

22470

AN:

53184

Middle Eastern (MID)

AF:

0.527

AC:

3037

AN:

5764

European-Non Finnish (NFE)

AF:

0.507

AC:

562969

AN:

1110058

Other (OTH)

AF:

0.483

AC:

29092

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

21382

42763

64145

85526

106908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16060

32120

48180

64240

80300

<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:

0.486

AC:

73806

AN:

152008

Hom.:

18684

Cov.:

AF XY:

0.478

AC XY:

35494

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.524

AC:

21737

AN:

41450

American (AMR)

AF:

0.420

AC:

6413

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2147

AN:

3468

East Asian (EAS)

AF:

0.0738

AC:

381

AN:

5166

South Asian (SAS)

AF:

0.458

AC:

2205

AN:

4816

European-Finnish (FIN)

AF:

0.414

AC:

4373

AN:

10556

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35046

AN:

67958

Other (OTH)

AF:

0.488

AC:

1030

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1928

3855

5783

7710

9638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.512

Hom.:

41899

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

- -

Systemic lupus erythematosus

Benign:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

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

(source)

DANN

Benign

0.77

PhyloP100

-0.39

Mutation Taster

=98/2

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