1-54999117-C-G

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.-70C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,581,328 control chromosomes in the GnomAD database, including 439,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35246 hom., cov: 33)
  • Exomes 𝑓: 0.75 (404317 hom.)
• Consequence: BSND NM_057176.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.06

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=-0.88).
• BP6: Variant 1-54999117-C-G is Benign according to our data. Variant chr1-54999117-C-G is described in ClinVar as [Benign]. Clinvar id is 297674.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/exons	MANE	UniProt
BSND	NM_057176.3	c.-70C>G		5_prime_UTR_variant	1/4	ENST00000651561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSND	ENST00000651561.1	c.-70C>G		5_prime_UTR_variant	1/4		NM_057176.3	P1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101800 AN: 151972 Hom.: 35240 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.747 AC: 1067966 AN: 1429238 Hom.: 404317 Cov.: 24 AF XY: 0.747 AC XY: 532516 AN XY: 712486

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.698

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.670 AC: 101853 AN: 152090 Hom.: 35246 Cov.: 33 AF XY: 0.662 AC XY: 49238 AN XY: 74350

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.668

Alfa AF: 0.662 Hom.: 2312

Bravo AF: 0.660

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bartter disease type 4A Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.3
Dann	Benign	0.64

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: rs2500341; hg19: chr1-55464790; COSMIC: COSV64871304;