Variant 8-11543119-C-G 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.-1-105C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,577,420 control chromosomes in the GnomAD database, including 236,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25363 hom., cov: 32)

Exomes 𝑓: 0.53 ( 211141 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.165

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:

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=-0.82).

BP6

Variant 8-11543119-C-G is Benign according to our data. Variant chr8-11543119-C-G is described in ClinVar as [Benign]. Clinvar id is 1192422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3 linkuse as main transcript	c.-1-105C>G		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
BLK	ENST00000259089.9 linkuse as main transcript	c.-1-105C>G	intron_variant	1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000645242.1 linkuse as main transcript	n.275-2933C>G	intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2 linkuse as main transcript	n.275-2933C>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

86054

AN:

151970

Hom.:

25329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.534

AC:

760882

AN:

1425332

Hom.:

211141

AF XY:

0.537

AC XY:

380549

AN XY:

708966

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.751

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.594

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.566

AC:

86139

AN:

152088

Hom.:

25363

Cov.:

AF XY:

0.580

AC XY:

43125

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.575

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.631

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.372

Hom.:

950

Bravo

AF:

0.574

Asia WGS

AF:

0.828

AC:

2875

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Maturity-onset diabetes of the young type 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Systemic lupus erythematosus

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

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 rs12386974, yet. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Benign

0.57

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