rs78904893

Positions:

• chr1-54999374-G-A
• chr1-54999374-G-T

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.177+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,600,054 control chromosomes in the GnomAD database, including 2,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (612 hom., cov: 32)
  • Exomes 𝑓: 0.030 (1945 hom.)
• Consequence: BSND NM_057176.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.532

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=-0.62).
• BP6: Variant 1-54999374-G-A is Benign according to our data. Variant chr1-54999374-G-A is described in ClinVar as [Benign]. Clinvar id is 46546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-54999374-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSND	NM_057176.3	c.177+11G>A		intron_variant		ENST00000651561.1	NP_476517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSND	ENST00000651561.1	c.177+11G>A		intron_variant			NM_057176.3	ENSP00000498282	P1

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10337 AN: 152120 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0742

GnomAD3 exomes AF: 0.0643 AC: 15698 AN: 244242 Hom.: 940 AF XY: 0.0576 AC XY: 7594 AN XY: 131880

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.0704

Gnomad FIN exome AF: 0.0236

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0578

GnomAD4 exome AF: 0.0300 AC: 43374 AN: 1447818 Hom.: 1945 Cov.: 32 AF XY: 0.0303 AC XY: 21762 AN XY: 717690

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.0499

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0686

Gnomad4 FIN exome AF: 0.0241

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0681 AC: 10361 AN: 152236 Hom.: 612 Cov.: 32 AF XY: 0.0685 AC XY: 5099 AN XY: 74438

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0338 Hom.: 89

Bravo AF: 0.0806

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	177+11G>A in Intron 01 of BSND: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 14.5% (543/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs78904893). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 29, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Bartter disease type 4A Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.9
DANN	Benign	0.82

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: rs78904893; hg19: chr1-55465047; COSMIC: COSV64870904;