rs34561376

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_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. 16/21 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:12

Conservation

PhyloP100: -0.290

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

Bartter disease type 4A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Bartter syndrome type 4
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BSND links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_057176.3

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	NM_057176.3	MANE Select	c.127G>A	p.Val43Ile	missense	Exon 1 of 4	NP_476517.1	Q8WZ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	ENST00000651561.1	MANE Select	c.127G>A	p.Val43Ile	missense	Exon 1 of 4	ENSP00000498282.1	Q8WZ55

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

GnomAD2 exomes

AF:

0.0270

AC:

6771

AN:

251122

AF XY:

0.0233

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 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

African (AFR)

AF:

0.136

AC:

4543

AN:

33478

American (AMR)

AF:

0.00819

AC:

366

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0229

AC:

599

AN:

26132

East Asian (EAS)

AF:

0.181

AC:

7182

AN:

39686

South Asian (SAS)

AF:

0.00879

AC:

758

AN:

86256

European-Finnish (FIN)

AF:

0.0000750

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000583

AC:

648

AN:

1111752

Other (OTH)

AF:

0.0193

AC:

1163

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

772

1545

2317

3090

3862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0451

AC:

6857

AN:

152136

Hom.:

445

Cov.:

AF XY:

0.0449

AC XY:

3336

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.130

AC:

5385

AN:

41480

American (AMR)

AF:

0.0150

AC:

229

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.183

AC:

937

AN:

5128

South Asian (SAS)

AF:

0.0139

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

68010

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

299

598

896

1195

1494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0219

Hom.:

459

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (3)

Bartter disease type 4A (1)

Bartter syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.49

(source)

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

PhyloP100

-0.29

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

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.034

gMVP

0.36

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over