rs117560775
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001146079.2(CLDN14):c.63G>A(p.Thr21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,585,838 control chromosomes in the GnomAD database, including 849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 75 hom., cov: 33)
Exomes 𝑓: 0.029 ( 774 hom. )
Consequence
CLDN14
NM_001146079.2 synonymous
NM_001146079.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.64
Genes affected
CLDN14 (HGNC:2035): (claudin 14) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. The encoded protein also binds specifically to the WW domain of Yes-associated protein. Defects in this gene are the cause of an autosomal recessive form of nonsyndromic sensorineural deafness. It is also reported that four synonymous variants in this gene are associated with kidney stones and reduced bone mineral density. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]
CLDN14-AS1 (HGNC:55953): (CLDN14 antisense RNA 1)
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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=-0.62).
BP6
?
Variant 21-36461633-C-T is Benign according to our data. Variant chr21-36461633-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 44087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.64 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN14 | NM_001146079.2 | c.63G>A | p.Thr21= | synonymous_variant | 2/2 | ENST00000399135.6 | |
CLDN14-AS1 | NR_183529.1 | n.468+15626C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN14 | ENST00000399135.6 | c.63G>A | p.Thr21= | synonymous_variant | 2/2 | 1 | NM_001146079.2 | P1 | |
CLDN14-AS1 | ENST00000428667.1 | n.277+15626C>T | intron_variant, non_coding_transcript_variant | 5 | |||||
LNCTSI | ENST00000429588.1 | n.54-18598C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0233 AC: 3540AN: 152084Hom.: 74 Cov.: 33
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GnomAD3 exomes AF: 0.0303 AC: 5988AN: 197896Hom.: 163 AF XY: 0.0293 AC XY: 3152AN XY: 107588
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GnomAD4 exome AF: 0.0290 AC: 41546AN: 1433636Hom.: 774 Cov.: 33 AF XY: 0.0287 AC XY: 20407AN XY: 711016
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GnomAD4 genome ? AF: 0.0233 AC: 3541AN: 152202Hom.: 75 Cov.: 33 AF XY: 0.0228 AC XY: 1697AN XY: 74400
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 10, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Thr21Thr in Exon 03 of CLDN14: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 2.8% (200/7018) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs117560775). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 16, 2018 | - - |
Autosomal recessive nonsyndromic hearing loss 29 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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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