rs199696535

Variant names:

• chr1-55008435-A-G
• rs199696535
• NM_057176.3:c.770A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_057176.3(BSND):​c.770A>G​(p.Gln257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: BSND NM_057176.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:6
• Conservation: PhyloP100: 0.415
• Publications: 0 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), ClinGen, 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047006845).

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.770A>G	p.Gln257Arg	missense	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.770A>G	p.Gln257Arg	missense	Exon 4 of 4	ENSP00000498282.1	Q8WZ55

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251176 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111984

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.41
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.27
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.72	P
Vest4		0.099
MVP		0.58
MPC		0.33
ClinPred		0.052	T
GERP RS		2.2
Varity_R		0.074
gMVP		0.053
Mutation Taster		=96/4	polymorphism

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: rs199696535; hg19: chr1-55474108;