rs34561376

Positions:

chr1-54999313-G-A

Variant summary

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

The NM_057176.3(BSND):c.127G>A(p.Val43Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,613,660 control chromosomes in the GnomAD database, including 1,460 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 445 hom., cov: 32)

Exomes 𝑓: 0.010 ( 1015 hom. )

Consequence

BSND
NM_057176.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.290

Variant links:

Genes affected

BSND (HGNC:16512): (barttin CLCNK type accessory subunit beta) This gene encodes an essential beta subunit for CLC chloride channels. These heteromeric channels localize to basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. Mutations in this gene have been associated with Bartter syndrome with sensorineural deafness. [provided by RefSeq, Jul 2008]

BSND 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 (MetaRNN=8.5645914E-4).

BP6

Variant 1-54999313-G-A is Benign according to our data. Variant chr1-54999313-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSND	NM_057176.3 linkuse as main transcript	c.127G>A	p.Val43Ile	missense_variant	1/4	ENST00000651561.1	NP_476517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSND	ENST00000651561.1 linkuse as main transcript	c.127G>A	p.Val43Ile	missense_variant	1/4		NM_057176.3	ENSP00000498282	P1

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6838

AN:

152018

Hom.:

443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0270

AC:

6771

AN:

251122

Hom.:

485

AF XY:

0.0233

AC XY:

3163

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.00720

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.00859

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.0105

AC:

15317

AN:

1461524

Hom.:

1015

Cov.:

AF XY:

0.00995

AC XY:

7231

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.00819

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.00879

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000583

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0451

AC:

6857

AN:

152136

Hom.:

445

Cov.:

AF XY:

0.0449

AC XY:

3336

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0157

Hom.:

221

Bravo

AF:

0.0522

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.123

AC:

543

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0279

AC:

3383

Asia WGS

AF:

0.0850

AC:

298

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Val43Ile in Exon 01 of BSND: This variant is not expected to have clinical signi ficance because it has been identified in 12.4% (462/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs34561376). -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 28, 2016	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bartter disease type 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Bartter syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.49

DANN

Benign

0.71

DEOGEN2

Benign

0.27

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.42

MetaRNN

Benign

0.00086

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.050

REVEL

Benign

0.046

Sift

Benign

0.75

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.015

MPC

0.066

ClinPred

0.00073

GERP RS

-2.8

Varity_R

0.034

gMVP

0.36

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