1-54999249-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_057176.3(BSND):​c.63C>T​(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,116 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 32 hom. )

Consequence

BSND
NM_057176.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.73
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 1-54999249-C-T is Benign according to our data. Variant chr1-54999249-C-T is described in ClinVar as [Benign]. Clinvar id is 46550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-54999249-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-3.73 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00122 (185/152244) while in subpopulation SAS AF= 0.0133 (64/4830). AF 95% confidence interval is 0.0106. There are 2 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BSNDNM_057176.3 linkuse as main transcriptc.63C>T p.Leu21= synonymous_variant 1/4 ENST00000651561.1 NP_476517.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BSNDENST00000651561.1 linkuse as main transcriptc.63C>T p.Leu21= synonymous_variant 1/4 NM_057176.3 ENSP00000498282 P1

Frequencies

GnomAD3 genomes
AF:
0.00120
AC:
183
AN:
152126
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000628
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0128
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000912
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00247
AC:
622
AN:
251422
Hom.:
9
AF XY:
0.00320
AC XY:
435
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.000861
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00456
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0128
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00101
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00156
AC:
2285
AN:
1461872
Hom.:
32
Cov.:
32
AF XY:
0.00205
AC XY:
1493
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000896
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.00398
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0144
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000594
Gnomad4 OTH exome
AF:
0.00194
GnomAD4 genome
AF:
0.00122
AC:
185
AN:
152244
Hom.:
2
Cov.:
33
AF XY:
0.00144
AC XY:
107
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0133
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000912
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00116
Hom.:
0
Bravo
AF:
0.00108
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.00174
EpiControl
AF:
0.00184

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024BSND: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJun 02, 2013The Leu21Leu variant in BSND: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 2% (4/196) of Tuscan c hromosomes by the 1000 Genome Project as well as in 0.1% (10/8600) of European A merican chromosomes and 0.1% (4/4406) of African American chromosomes by the NHL BI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs14161148 6). -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Bartter disease type 4A Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Bartter syndrome Benign:1
Likely benign, no assertion criteria providedclinical testingNatera, Inc.Oct 23, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.19
DANN
Benign
0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141611486; hg19: chr1-55464922; API