rs78904893

Variant names:

• chr1-54999374-G-A
• rs78904893
• NM_057176.3:c.177+11G>A

Your query was ambiguous. Multiple possible variants found:

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

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.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
• Publications: 5 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, PanelApp Australia
• 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=-0.62).
• BP6: Variant 1-54999374-G-A is Benign according to our data. Variant chr1-54999374-G-A is described in ClinVar as Benign. ClinVar VariationId is 46546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 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.177+11G>A		intron	N/A	NP_476517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	ENST00000651561.1	MANE Select	c.177+11G>A		intron	N/A	ENSP00000498282.1

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

GnomAD2 exomes AF: 0.0643 AC: 15698 AN: 244242 AF XY: 0.0576

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 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

African (AFR) AF: 0.154 AC: 5125 AN: 33262

American (AMR) AF: 0.159 AC: 7075 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 1282 AN: 25682

East Asian (EAS) AF: 0.144 AC: 5671 AN: 39388

South Asian (SAS) AF: 0.0686 AC: 5857 AN: 85406

European-Finnish (FIN) AF: 0.0241 AC: 1254 AN: 52048

Middle Eastern (MID) AF: 0.0850 AC: 467 AN: 5494

European-Non Finnish (NFE) AF: 0.0127 AC: 13958 AN: 1102480

Other (OTH) AF: 0.0450 AC: 2685 AN: 59674

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

African (AFR) AF: 0.148 AC: 6163 AN: 41534

American (AMR) AF: 0.101 AC: 1548 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.126 AC: 648 AN: 5148

South Asian (SAS) AF: 0.0740 AC: 357 AN: 4826

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10626

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1032 AN: 68014

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0358 Hom.: 100

Bravo AF: 0.0806

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.9
DANN	Benign	0.82
PhyloP100		-0.53
PromoterAI		0.029	Neutral
Mutation Taster		=100/0	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: rs78904893; hg19: chr1-55465047; COSMIC: COSV64870904;