rs33938617

Variant names:

• chr1-55008589-G-A
• rs33938617
• NM_057176.3:c.924G>A
• BSND p.Pro308Pro

Your query was ambiguous. Multiple possible variants found:

• chr1-55008589-G-A
• chr1-55008589-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_057176.3(BSND):​c.924G>A​(p.Pro308Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,940 control chromosomes in the GnomAD database, including 31,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P308P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.18 (2695 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28612 hom.)
• Consequence: BSND NM_057176.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -3.67
• Publications: 12 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-55008589-G-A is Benign according to our data. Variant chr1-55008589-G-A is described in ClinVar as Benign. ClinVar VariationId is 46553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 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.924G>A	p.Pro308Pro	synonymous	Exon 4 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.924G>A	p.Pro308Pro	synonymous	Exon 4 of 4	ENSP00000498282.1	Q8WZ55

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27167 AN: 151960 Hom.: 2688 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.151 AC: 37999 AN: 250858 AF XY: 0.152

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.0822

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.191 AC: 279283 AN: 1461862 Hom.: 28612 Cov.: 34 AF XY: 0.187 AC XY: 136184 AN XY: 727238

African (AFR) AF: 0.189 AC: 6317 AN: 33480

American (AMR) AF: 0.0872 AC: 3898 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2904 AN: 26136

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39700

South Asian (SAS) AF: 0.0849 AC: 7322 AN: 86256

European-Finnish (FIN) AF: 0.169 AC: 9000 AN: 53408

Middle Eastern (MID) AF: 0.111 AC: 643 AN: 5768

European-Non Finnish (NFE) AF: 0.215 AC: 238743 AN: 1111994

Other (OTH) AF: 0.173 AC: 10442 AN: 60396

GnomAD4 genome AF: 0.179 AC: 27190 AN: 152078 Hom.: 2695 Cov.: 32 AF XY: 0.172 AC XY: 12750 AN XY: 74340

African (AFR) AF: 0.189 AC: 7843 AN: 41454

American (AMR) AF: 0.111 AC: 1703 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3466

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5164

South Asian (SAS) AF: 0.0821 AC: 396 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14481 AN: 67976

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.181 Hom.: 1775

Bravo AF: 0.176

Asia WGS AF: 0.0360 AC: 126 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.201

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Bartter disease type 4A (3)
-	-	2	not provided (2)
-	-	1	Bartter syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.022
DANN	Benign	0.33
PhyloP100		-3.7
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs33938617;

hg19: chr1-55474262;

COSMIC: COSV64870714;