rs200886926

chr1-55008262-T-C

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.597T>C(p.Asp199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,614,200 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (8 hom.)
• Consequence: BSND NM_057176.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.247

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=-0.6).
• BP6: Variant 1-55008262-T-C is Benign according to our data. Variant chr1-55008262-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 226466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000398 (582/1461888) while in subpopulation AMR AF= 0.0129 (576/44724). AF 95% confidence interval is 0.012. There are 8 homozygotes in gnomad4_exome. There are 229 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSND	NM_057176.3	c.597T>C	p.Asp199=	synonymous_variant	4/4	ENST00000651561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSND	ENST00000651561.1	c.597T>C	p.Asp199=	synonymous_variant	4/4		NM_057176.3	P1

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00211 AC: 530 AN: 251050 Hom.: 8 AF XY: 0.00148 AC XY: 201 AN XY: 135754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000398 AC: 582 AN: 1461888 Hom.: 8 Cov.: 31 AF XY: 0.000315 AC XY: 229 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74486

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000228 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bartter disease type 4A Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 08, 2015

p.Asp199Asp in exon 4 of BSND: This variant is not expected to have clinical sig nificance it has been identified in 1.8% (207/11524) of Latino chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs20 0886926). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	6.5
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200886926; hg19: chr1-55473935;