rs141611486

chr1-54999249-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_057176.3(BSND):c.63C>T(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,116 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (32 hom.)
• Consequence: BSND NM_057176.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.73

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-54999249-C-T is Benign according to our data. Variant chr1-54999249-C-T is described in ClinVar as [Benign]. Clinvar id is 46550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-54999249-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-3.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00122 (185/152244) while in subpopulation SAS AF= 0.0133 (64/4830). AF 95% confidence interval is 0.0106. There are 2 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSND	NM_057176.3	c.63C>T	p.Leu21=	synonymous_variant	1/4	ENST00000651561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSND	ENST00000651561.1	c.63C>T	p.Leu21=	synonymous_variant	1/4		NM_057176.3	P1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152126 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00247 AC: 622 AN: 251422 Hom.: 9 AF XY: 0.00320 AC XY: 435 AN XY: 135898

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00456

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00156 AC: 2285 AN: 1461872 Hom.: 32 Cov.: 32 AF XY: 0.00205 AC XY: 1493 AN XY: 727242

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00398

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000594

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152244 Hom.: 2 Cov.: 33 AF XY: 0.00144 AC XY: 107 AN XY: 74446

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00108

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	BSND: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 02, 2013	The Leu21Leu variant in BSND: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 2% (4/196) of Tuscan c hromosomes by the 1000 Genome Project as well as in 0.1% (10/8600) of European A merican chromosomes and 0.1% (4/4406) of African American chromosomes by the NHL BI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs14161148 6). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Bartter disease type 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Oct 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.19
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs141611486; hg19: chr1-55464922;