NM_001366385.1:c.1778T>A
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_001366385.1(CARD14):c.1778T>A(p.Ile593Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001366385.1 missense
Scores
Clinical Significance
Conservation
Publications
- familial pityriasis rubra pilarisInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
- psoriasis 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.1778T>A | p.Ile593Asn | missense_variant | Exon 16 of 24 | ENST00000648509.2 | NP_001353314.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 250306 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460928Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726800 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:1Other:1
Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with psoriasis and in unaffected controls in published literature (Jordan et al., 2012); This variant is associated with the following publications: (PMID: 27939769, 30386326, 22521419) -
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Pityriasis rubra pilaris Uncertain:1
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. -
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 593 of the CARD14 protein (p.Ile593Asn). This variant is present in population databases (rs281875220, gnomAD 0.0009%). This missense change has been observed in individual(s) with psoriasis (PMID: 22521419). ClinVar contains an entry for this variant (Variation ID: 68776). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CARD14 protein function. Experimental studies have shown that this missense change does not substantially affect CARD14 function (PMID: 22421419). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at