dbSNP rs62490888: BLK:n.925G>A (chr8-11561257-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000526097.1(BLK):n.925G>A 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 0.125 in 1,596,468 control chromosomes in the GnomAD database, including 13,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1032 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12323 hom. )

Consequence

BLK
ENST00000526097.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.97

Publications

9 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.024).

BP6

Variant 8-11561257-G-A is Benign according to our data. Variant chr8-11561257-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.1030-45G>A		intron_variant	Intron 10 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.1030-45G>A		intron_variant	Intron 10 of 12	1	NM_001715.3	ENSP00000259089.4		P51451

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16030

AN:

152144

Hom.:

1034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0460

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0334

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.121

AC:

26909

AN:

223218

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.0325

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.127

AC:

183160

AN:

1444206

Hom.:

12323

Cov.:

AF XY:

0.128

AC XY:

91484

AN XY:

716790

show subpopulations

African (AFR)

AF:

0.0406

AC:

1343

AN:

33070

American (AMR)

AF:

0.104

AC:

4419

AN:

42324

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2676

AN:

25870

East Asian (EAS)

AF:

0.0243

AC:

940

AN:

38666

South Asian (SAS)

AF:

0.144

AC:

12052

AN:

83480

European-Finnish (FIN)

AF:

0.168

AC:

8756

AN:

52168

Middle Eastern (MID)

AF:

0.110

AC:

630

AN:

5752

European-Non Finnish (NFE)

AF:

0.132

AC:

145680

AN:

1103120

Other (OTH)

AF:

0.112

AC:

6664

AN:

59756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

9330

18659

27989

37318

46648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5160

10320

15480

20640

25800

<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:

0.105

AC:

16024

AN:

152262

Hom.:

1032

Cov.:

AF XY:

0.108

AC XY:

8025

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0459

AC:

1908

AN:

41564

American (AMR)

AF:

0.0970

AC:

1485

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

347

AN:

3470

East Asian (EAS)

AF:

0.0333

AC:

172

AN:

5162

South Asian (SAS)

AF:

0.140

AC:

676

AN:

4824

European-Finnish (FIN)

AF:

0.180

AC:

1916

AN:

10618

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9207

AN:

68002

Other (OTH)

AF:

0.102

AC:

215

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

743

1486

2228

2971

3714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.123

Hom.:

1706

Bravo

AF:

0.0961

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 09, 2018

GeneDx

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

-0.88

CADD

Benign

0.017

(source)

DANN

Uncertain

0.99

PhyloP100

-2.0

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