rs12069526

Variant names:

• chr1-54998946-G-A
• rs12069526
• NM_057176.3:c.-241G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

BSND Gene-Disease associations (from GenCC):

• Bartter disease type 4A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• Bartter syndrome type 4

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	NM_057176.3	MANE Select	c.-241G>A		5_prime_UTR	Exon 1 of 4	NP_476517.1	Q8WZ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	ENST00000651561.1	MANE Select	c.-241G>A		5_prime_UTR	Exon 1 of 4	ENSP00000498282.1	Q8WZ55

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

African (AFR) AF: 0.129 AC: 1477 AN: 11408

American (AMR) AF: 0.0101 AC: 171 AN: 16892

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 258 AN: 12066

East Asian (EAS) AF: 0.177 AC: 4753 AN: 26906

South Asian (SAS) AF: 0.00910 AC: 376 AN: 41308

European-Finnish (FIN) AF: 0.0000394 AC: 1 AN: 25354

Middle Eastern (MID) AF: 0.00644 AC: 11 AN: 1708

European-Non Finnish (NFE) AF: 0.000778 AC: 184 AN: 236418

Other (OTH) AF: 0.0217 AC: 495 AN: 22822

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

African (AFR) AF: 0.130 AC: 5406 AN: 41568

American (AMR) AF: 0.0148 AC: 227 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.183 AC: 946 AN: 5170

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000867 AC: 59 AN: 68036

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0196 Hom.: 86

Bravo AF: 0.0522

Asia WGS AF: 0.0840 AC: 295 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bartter disease type 4A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.57
PhyloP100		-0.050
PromoterAI		0.12	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12069526; hg19: chr1-55464619;