Genetic Variant BLK:n.274+2613T>G (chr8-11489780-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000645242.1(BLK):n.274+2613T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,964 control chromosomes in the GnomAD database, including 18,050 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 0.47 ( 18050 hom., cov: 32)

Consequence

BLK
ENST00000645242.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516

Publications

16 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:

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new If you want to explore the variant's impact on the transcript ENST00000645242.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645242.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000645242.1		n.274+2613T>G		intron	N/A
	BLK	ENST00000696154.2		n.274+2613T>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71637

AN:

151846

Hom.:

18029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.472

AC:

71707

AN:

151964

Hom.:

18050

Cov.:

AF XY:

0.458

AC XY:

34001

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.478

AC:

19813

AN:

41424

American (AMR)

AF:

0.353

AC:

5382

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2025

AN:

3472

East Asian (EAS)

AF:

0.00559

AC:

AN:

5184

South Asian (SAS)

AF:

0.365

AC:

1759

AN:

4816

European-Finnish (FIN)

AF:

0.392

AC:

4130

AN:

10540

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37098

AN:

67950

Other (OTH)

AF:

0.469

AC:

989

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1834

3668

5502

7336

9170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.436

Hom.:

2291

Bravo

AF:

0.463

Asia WGS

AF:

0.201

AC:

699

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

(source)

DANN

Benign

0.49

PhyloP100

0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over