Variant chr8-11543171-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001715.3(BLK):c.-1-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,610,296 control chromosomes in the GnomAD database, including 176,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13810 hom., cov: 31)

Exomes 𝑓: 0.46 ( 163156 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.369

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-11543171-G-A is Benign according to our data. Variant chr8-11543171-G-A is described in ClinVar as [Benign]. Clinvar id is 1192423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.-1-53G>A		intron_variant	Intron 1 of 12	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLK	ENST00000259089.9 link	c.-1-53G>A	intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4	P51451
BLK	ENST00000645242.1 link	n.275-2881G>A	intron_variant	Intron 1 of 11
BLK	ENST00000696154.2 link	n.275-2881G>A	intron_variant	Intron 1 of 11				A0A8Q3SIE3

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62361

AN:

151882

Hom.:

13808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.426

GnomAD4 exome

AF:

0.460

AC:

671426

AN:

1458296

Hom.:

163156

AF XY:

0.458

AC XY:

332016

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.410

AC:

62367

AN:

152000

Hom.:

13810

Cov.:

AF XY:

0.397

AC XY:

29509

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.00521

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.475

Hom.:

2210

Bravo

AF:

0.400

Asia WGS

AF:

0.164

AC:

574

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Maturity-onset diabetes of the young type 11

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Systemic lupus erythematosus

Benign:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

BLK gene is associated with Systemic lupus erythematosus, sjogren's syndrome and other systemic inflammatory conditions. However no sufficient evidence is found to ascertain the role of this particular variant rs2245250, yet. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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