1-55007183-C-T

Variant names:

• chr1-55007183-C-T
• rs138974602
• NM_057176.3:c.459C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_057176.3(BSND):​c.459C>T​(p.Asp153Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,614,168 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (16 hom.)
• Consequence: BSND NM_057176.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.34
• 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: 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-55007183-C-T is Benign according to our data. Variant chr1-55007183-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00311 (473/152276) while in subpopulation NFE AF = 0.00473 (322/68028). AF 95% confidence interval is 0.00431. There are 0 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

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.459C>T	p.Asp153Asp	synonymous	Exon 3 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.459C>T	p.Asp153Asp	synonymous	Exon 3 of 4	ENSP00000498282.1	Q8WZ55

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 473 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00297 AC: 747 AN: 251404 AF XY: 0.00295

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.00474

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00416 AC: 6076 AN: 1461892 Hom.: 16 Cov.: 33 AF XY: 0.00415 AC XY: 3015 AN XY: 727246

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00273 AC: 122 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00416 AC: 222 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00493 AC: 5484 AN: 1112012

Other (OTH) AF: 0.00359 AC: 217 AN: 60396

GnomAD4 genome AF: 0.00311 AC: 473 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74448

African (AFR) AF: 0.000987 AC: 41 AN: 41550

American (AMR) AF: 0.00412 AC: 63 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00473 AC: 322 AN: 68028

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00287 Hom.: 1

Bravo AF: 0.00287

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00436

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.0
DANN	Benign	0.43
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs138974602; hg19: chr1-55472856; COSMIC: COSV64870190;