chr10-96230827-A-G

Position:

chr10-96230827-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013314.4(BLNK):c.171T>C(p.Pro57Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,609,256 control chromosomes in the GnomAD database, including 384,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28143 hom., cov: 31)

Exomes 𝑓: 0.69 ( 356735 hom. )

Consequence

BLNK
NM_013314.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.102

Variant links:

Genes affected

BLNK (HGNC:14211): (B cell linker) This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

BLNK links:

BLNK (HGNC:):

BLNK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-96230827-A-G is Benign according to our data. Variant chr10-96230827-A-G is described in ClinVar as [Benign]. Clinvar id is 402427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-96230827-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLNK	NM_013314.4 linkuse as main transcript	c.171T>C	p.Pro57Pro	synonymous_variant	4/17	ENST00000224337.10	NP_037446.1	Q8WV28-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLNK	ENST00000224337.10 linkuse as main transcript	c.171T>C	p.Pro57Pro	synonymous_variant	4/17	1	NM_013314.4	ENSP00000224337.6		Q8WV28-1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86256

AN:

151908

Hom.:

28148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.675

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.580

GnomAD3 exomes

AF:

0.640

AC:

155908

AN:

243678

Hom.:

52407

AF XY:

0.640

AC XY:

84067

AN XY:

131376

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.739

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.668

GnomAD4 exome

AF:

0.692

AC:

1008599

AN:

1457230

Hom.:

356735

Cov.:

AF XY:

0.687

AC XY:

497802

AN XY:

724264

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.708

Gnomad4 ASJ exome

AF:

0.675

Gnomad4 EAS exome

AF:

0.497

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.737

Gnomad4 NFE exome

AF:

0.728

Gnomad4 OTH exome

AF:

0.654

GnomAD4 genome

AF:

0.567

AC:

86263

AN:

152026

Hom.:

28143

Cov.:

AF XY:

0.568

AC XY:

42220

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.675

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.493

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.577

Alfa

AF:

0.687

Hom.:

69973

Bravo

AF:

0.551

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

Agammaglobulinemia 4, autosomal recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.63

DANN

Benign

0.50

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