dbSNP rs62490888: BLK:c.1030-45G>A (chr8-11561257-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001715.3(BLK):c.1030-45G>A variant causes a intron 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
NM_001715.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.97

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 links:

ENSG00000269954 (HGNC:58190):

ENSG00000269954 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-11561257-G-A is Benign according to our data. Variant chr8-11561257-G-A is described in ClinVar as [Benign]. Clinvar id 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

GnomAD3 exomes

AF:

0.121

AC:

26909

AN:

223218

Hom.:

1781

AF XY:

0.123

AC XY:

14855

AN XY:

120436

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 SAS exome

AF:

0.145

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

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0243

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.105

AC:

16024

AN:

152262

Hom.:

1032

Cov.:

AF XY:

0.108

AC XY:

8025

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.0970

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.180

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.110

Hom.:

176

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

DANN

Uncertain

0.99

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over