1-54999249-C-T
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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
NM_057176.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.73
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]
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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 |
---|---|---|---|---|---|---|---|---|
BSND | NM_057176.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
BSND | ENST00000651561.1 | c.63C>T | p.Leu21= | synonymous_variant | 1/4 | NM_057176.3 | ENSP00000498282 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00120 AC: 183AN: 152126Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00247 AC: 622AN: 251422Hom.: 9 AF XY: 0.00320 AC XY: 435AN XY: 135898
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GnomAD4 exome AF: 0.00156 AC: 2285AN: 1461872Hom.: 32 Cov.: 32 AF XY: 0.00205 AC XY: 1493AN XY: 727242
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GnomAD4 genome AF: 0.00122 AC: 185AN: 152244Hom.: 2 Cov.: 33 AF XY: 0.00144 AC XY: 107AN XY: 74446
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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 submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | BSND: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 02, 2013 | The 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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Bartter disease type 4A Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This 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 provided | clinical testing | Natera, Inc. | Oct 23, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at