Genetic Variant BLK:c.473-1714C>T (chr8-11553029-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001715.3(BLK):c.473-1714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 162,476 control chromosomes in the GnomAD database, including 73,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.95 ( 68529 hom., cov: 37)

Exomes 𝑓: 0.98 ( 4917 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.473-1714C>T		intron_variant	Intron 6 of 12	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9 link	c.473-1714C>T		intron_variant	Intron 6 of 12	1	NM_001715.3	ENSP00000259089.4		P51451

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

144037

AN:

152204

Hom.:

68486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.965

Gnomad ASJ

AF:

0.947

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.987

Gnomad OTH

AF:

0.944

GnomAD4 exome

AF:

0.984

AC:

9991

AN:

10154

Hom.:

4917

Cov.:

AF XY:

0.985

AC XY:

5190

AN XY:

5268

show subpopulations

African (AFR)

AF:

0.831

AC:

221

AN:

266

American (AMR)

AF:

0.972

AC:

770

AN:

792

Ashkenazi Jewish (ASJ)

AF:

0.951

AC:

251

AN:

264

East Asian (EAS)

AF:

1.00

AC:

400

AN:

400

South Asian (SAS)

AF:

0.998

AC:

912

AN:

914

European-Finnish (FIN)

AF:

1.00

AC:

446

AN:

446

Middle Eastern (MID)

AF:

0.905

AC:

AN:

European-Non Finnish (NFE)

AF:

0.991

AC:

6356

AN:

6414

Other (OTH)

AF:

0.973

AC:

568

AN:

584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.946

AC:

144138

AN:

152322

Hom.:

68529

Cov.:

AF XY:

0.948

AC XY:

70596

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.846

AC:

35142

AN:

41554

American (AMR)

AF:

0.965

AC:

14768

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

3288

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5188

AN:

5192

South Asian (SAS)

AF:

0.995

AC:

4803

AN:

4828

European-Finnish (FIN)

AF:

0.998

AC:

10608

AN:

10624

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.987

AC:

67162

AN:

68026

Other (OTH)

AF:

0.945

AC:

1999

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

384

769

1153

1538

1922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.966

Hom.:

8843

Bravo

AF:

0.941

Asia WGS

AF:

0.984

AC:

3421

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.71

(source)

DANN

Benign

0.50

PhyloP100

-1.1

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

Computational scores

Splicing

Publications

Other links and lift over