1-55005136-G-A

Variant names:

• chr1-55005136-G-A
• rs79445756
• NM_057176.3:c.272+20G>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.272+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,612,026 control chromosomes in the GnomAD database, including 799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (400 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (399 hom.)
• Consequence: BSND NM_057176.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.560
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-55005136-G-A is Benign according to our data. Variant chr1-55005136-G-A is described in ClinVar as Benign. ClinVar VariationId is 262299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.272+20G>A		intron	N/A	NP_476517.1	Q8WZ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	ENST00000651561.1	MANE Select	c.272+20G>A		intron	N/A	ENSP00000498282.1	Q8WZ55

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6260 AN: 152188 Hom.: 396 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0368

GnomAD2 exomes AF: 0.0110 AC: 2738 AN: 249576 AF XY: 0.00814

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.00774

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000497

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00461 AC: 6725 AN: 1459720 Hom.: 399 Cov.: 30 AF XY: 0.00396 AC XY: 2876 AN XY: 726286

African (AFR) AF: 0.148 AC: 4956 AN: 33440

American (AMR) AF: 0.00852 AC: 381 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 269 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000372 AC: 32 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53166

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5766

European-Non Finnish (NFE) AF: 0.000353 AC: 392 AN: 1110394

Other (OTH) AF: 0.0106 AC: 637 AN: 60330

GnomAD4 genome AF: 0.0412 AC: 6282 AN: 152306 Hom.: 400 Cov.: 33 AF XY: 0.0401 AC XY: 2987 AN XY: 74474

African (AFR) AF: 0.142 AC: 5891 AN: 41568

American (AMR) AF: 0.0152 AC: 233 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68016

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

Alfa AF: 0.0201 Hom.: 50

Bravo AF: 0.0475

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.65
PhyloP100		-0.56
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: rs79445756; hg19: chr1-55470809;