1-54998946-G-A

Position:

• chr1-54998946-G-A

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.-241G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 547,208 control chromosomes in the GnomAD database, including 993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (446 hom., cov: 33)
  • Exomes 𝑓: 0.020 (547 hom.)
• Consequence: BSND NM_057176.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0500

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=-0.6).
• BP6: Variant 1-54998946-G-A is Benign according to our data. Variant chr1-54998946-G-A is described in ClinVar as [Benign]. Clinvar id is 297670.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSND	NM_057176.3	c.-241G>A		5_prime_UTR_variant	1/4	ENST00000651561.1	NP_476517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSND	ENST00000651561.1	c.-241G>A		5_prime_UTR_variant	1/4		NM_057176.3	ENSP00000498282	P1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6850 AN: 152208 Hom.: 444 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.0196 AC: 7726 AN: 394882 Hom.: 547 Cov.: 3 AF XY: 0.0183 AC XY: 3798 AN XY: 207056

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.00910

Gnomad4 FIN exome AF: 0.0000394

Gnomad4 NFE exome AF: 0.000778

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0451 AC: 6869 AN: 152326 Hom.: 446 Cov.: 33 AF XY: 0.0449 AC XY: 3346 AN XY: 74496

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0182 Hom.: 54

Bravo AF: 0.0522

Asia WGS AF: 0.0840 AC: 295 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.57

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: rs12069526; hg19: chr1-55464619;