NM_057176.3:c.-117T>C

Variant names:

• chr1-54999070-T-C
• rs2500340
• NM_057176.3:c.-117T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_057176.3(BSND):​c.-117T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,292,140 control chromosomes in the GnomAD database, including 355,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35230 hom., cov: 33)
  • Exomes 𝑓: 0.74 (319949 hom.)
• Consequence: BSND NM_057176.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.360

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-54999070-T-C is Benign according to our data. Variant chr1-54999070-T-C is described in ClinVar as [Benign]. Clinvar id is 297673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSND	NM_057176.3	c.-117T>C		5_prime_UTR_variant	Exon 1 of 4	ENST00000651561.1	NP_476517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSND	ENST00000651561	c.-117T>C		5_prime_UTR_variant	Exon 1 of 4		NM_057176.3	ENSP00000498282.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101769 AN: 151972 Hom.: 35224 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.744 AC: 847818 AN: 1140050 Hom.: 319949 Cov.: 15 AF XY: 0.744 AC XY: 427769 AN XY: 574804

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.669 AC: 101822 AN: 152090 Hom.: 35230 Cov.: 33 AF XY: 0.662 AC XY: 49215 AN XY: 74346

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.667

Alfa AF: 0.743 Hom.: 41321

Bravo AF: 0.659

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bartter disease type 4A Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	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

Other links and lift over

dbSNP: rs2500340; hg19: chr1-55464743; COSMIC: COSV64870665;