rs1042695

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000526097.1(BLK):n.1796T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 562,732 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 35)

Exomes 𝑓: 0.0059 ( 16 hom. )

Consequence

BLK
ENST00000526097.1 non_coding_transcript_exon

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:1

Conservation

PhyloP100: -1.33

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-11564446-T-G is Benign according to our data. Variant chr8-11564446-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 12320.

BS2

High AC in GnomAd4 at 631 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.*338T>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9 link	c.*338T>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_001715.3	ENSP00000259089.4		P51451

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

630

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00545

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00636

AC:

820

AN:

128888

AF XY:

0.00636

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.000959

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00501

GnomAD4 exome

AF:

0.00589

AC:

2419

AN:

410386

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

1392

AN XY:

226162

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

12428

American (AMR)

AF:

0.00404

AC:

122

AN:

30188

Ashkenazi Jewish (ASJ)

AF:

0.0270

AC:

416

AN:

15392

East Asian (EAS)

AF:

0.000517

AC:

AN:

19354

South Asian (SAS)

AF:

0.00763

AC:

463

AN:

60664

European-Finnish (FIN)

AF:

0.000452

AC:

AN:

19924

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

3382

European-Non Finnish (NFE)

AF:

0.00521

AC:

1184

AN:

227282

Other (OTH)

AF:

0.00652

AC:

142

AN:

21772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

280

419

559

699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00414

AC:

631

AN:

152346

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

306

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41586

American (AMR)

AF:

0.00366

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.00539

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00545

AC:

371

AN:

68024

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00750

Hom.:

Bravo

AF:

0.00436

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Maturity-onset diabetes of the young type 11

Pathogenic:1Benign:1

Aug 25, 2009

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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. -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.7

(source)

DANN

Benign

0.27

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(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