Genetic Variant NM_001715.3:c.1313-28C>T (chr8-11563875-C-T) – 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.1313-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,594,148 control chromosomes in the GnomAD database, including 133,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14801 hom., cov: 34)

Exomes 𝑓: 0.39 ( 118985 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.858

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=-0.86).

BP6

Variant 8-11563875-C-T is Benign according to our data. Variant chr8-11563875-C-T is described in ClinVar as [Benign]. Clinvar id is 1192495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.1313-28C>T		intron_variant	Intron 12 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.1313-28C>T		intron_variant	Intron 12 of 12	1	NM_001715.3	ENSP00000259089.4		P51451

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64707

AN:

152038

Hom.:

14772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.923

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.468

AC:

96928

AN:

206998

Hom.:

25315

AF XY:

0.460

AC XY:

53055

AN XY:

115252

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.921

Gnomad SAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.393

AC:

566106

AN:

1441992

Hom.:

118985

Cov.:

AF XY:

0.394

AC XY:

282020

AN XY:

716564

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.918

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.426

AC:

64785

AN:

152156

Hom.:

14801

Cov.:

AF XY:

0.436

AC XY:

32395

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.434

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.924

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.379

Hom.:

2101

Bravo

AF:

0.440

Asia WGS

AF:

0.694

AC:

2411

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 09, 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 rs10097015, yet. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.1

DANN

Benign

0.90

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