rs113831133
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_001146079.2(CLDN14):c.11C>T(p.Thr4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,551,856 control chromosomes in the GnomAD database, including 843 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T4T) has been classified as Likely benign.
Frequency
Consequence
NM_001146079.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN14 | NM_001146079.2 | c.11C>T | p.Thr4Met | missense_variant | 2/2 | ENST00000399135.6 | |
CLDN14-AS1 | NR_183529.1 | n.468+15678G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN14 | ENST00000399135.6 | c.11C>T | p.Thr4Met | missense_variant | 2/2 | 1 | NM_001146079.2 | P1 | |
CLDN14-AS1 | ENST00000428667.1 | n.277+15678G>A | intron_variant, non_coding_transcript_variant | 5 | |||||
LNCTSI | ENST00000429588.1 | n.54-18546G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0436 AC: 6633AN: 152210Hom.: 272 Cov.: 33
GnomAD3 exomes AF: 0.0245 AC: 3678AN: 150242Hom.: 84 AF XY: 0.0248 AC XY: 1998AN XY: 80574
GnomAD4 exome AF: 0.0233 AC: 32587AN: 1399528Hom.: 571 Cov.: 33 AF XY: 0.0233 AC XY: 16078AN XY: 690658
GnomAD4 genome ? AF: 0.0436 AC: 6642AN: 152328Hom.: 272 Cov.: 33 AF XY: 0.0417 AC XY: 3110AN XY: 74498
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Thr4Met in Exon 03 of CLDN14: This variant is not expected to have clinical sign ificance because it has been identified in 9.1% (328/3592) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs113831133). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 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 | Eurofins Ntd Llc (ga) | Mar 02, 2017 | - - |
Autosomal recessive nonsyndromic hearing loss 29 Benign:2
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at