rs113350364
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001146079.2(CLDN14):c.300C>T(p.Ile100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,192 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 34 hom. )
Consequence
CLDN14
NM_001146079.2 synonymous
NM_001146079.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.35
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=-0.85).
BP6
?
Variant 21-36461396-G-A is Benign according to our data. Variant chr21-36461396-G-A is described in ClinVar as [Benign]. Clinvar id is 178603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.35 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00189 (288/152356) while in subpopulation SAS AF= 0.0159 (77/4828). AF 95% confidence interval is 0.0131. There are 1 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 34 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN14 | NM_001146079.2 | c.300C>T | p.Ile100= | synonymous_variant | 2/2 | ENST00000399135.6 | |
CLDN14-AS1 | NR_183529.1 | n.468+15389G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN14 | ENST00000399135.6 | c.300C>T | p.Ile100= | synonymous_variant | 2/2 | 1 | NM_001146079.2 | P1 | |
CLDN14-AS1 | ENST00000428667.1 | n.277+15389G>A | intron_variant, non_coding_transcript_variant | 5 | |||||
LNCTSI | ENST00000429588.1 | n.54-18835G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00184 AC: 280AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00347 AC: 860AN: 247656Hom.: 13 AF XY: 0.00412 AC XY: 553AN XY: 134208
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GnomAD4 exome AF: 0.00173 AC: 2525AN: 1460836Hom.: 34 Cov.: 34 AF XY: 0.00218 AC XY: 1584AN XY: 726756
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GnomAD4 genome ? AF: 0.00189 AC: 288AN: 152356Hom.: 1 Cov.: 33 AF XY: 0.00239 AC XY: 178AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 06, 2019 | This variant is associated with the following publications: (PMID: 15880785, 23590985) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 15, 2019 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 21, 2016 | p.Ile100Ile in Exon 03 of CLDN14: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 1.6% (267/16490) o f South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs113350364). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 11, 2016 | - - |
Autosomal recessive nonsyndromic hearing loss 29 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Aug 25, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
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