Variant chr8-11558088-C-T 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.1029+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,576,564 control chromosomes in the GnomAD database, including 275,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25763 hom., cov: 33)

Exomes 𝑓: 0.58 ( 250147 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.51

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:

LOC105379241 (HGNC:):

LOC105379241 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=-0.89).

BP6

Variant 8-11558088-C-T is Benign according to our data. Variant chr8-11558088-C-T is described in ClinVar as [Benign]. Clinvar id is 1253200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 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.1029+50C>T		intron_variant		ENST00000259089.9	NP_001706.2
LOC105379241	XR_948956.3 linkuse as main transcript	n.178G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
BLK	ENST00000259089.9 linkuse as main transcript	c.1029+50C>T	intron_variant	1	NM_001715.3	ENSP00000259089	P1
	ENST00000602626.2 linkuse as main transcript	n.242-110G>A	intron_variant, non_coding_transcript_variant
BLK	ENST00000645242.1 linkuse as main transcript	n.1180+50C>T	intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2 linkuse as main transcript	n.1137+34C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86623

AN:

151952

Hom.:

25759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.0586

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.520

AC:

129183

AN:

248324

Hom.:

36816

AF XY:

0.523

AC XY:

70178

AN XY:

134224

show subpopulations

Gnomad AFR exome

AF:

0.624

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.659

Gnomad EAS exome

AF:

0.0602

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.583

AC:

830270

AN:

1424494

Hom.:

250147

Cov.:

AF XY:

0.581

AC XY:

412992

AN XY:

710888

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.0570

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.570

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.570

AC:

86661

AN:

152070

Hom.:

25763

Cov.:

AF XY:

0.558

AC XY:

41510

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.653

Gnomad4 EAS

AF:

0.0583

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.618

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.615

Hom.:

5432

Bravo

AF:

0.560

Asia WGS

AF:

0.275

AC:

962

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

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.31

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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