17-80188479-G-A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBS1_SupportingBS2_Supporting
The NM_001366385.1(CARD14):c.778G>A(p.Gly260Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,590,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.778G>A | p.Gly260Arg | missense_variant | Exon 8 of 24 | ENST00000648509.2 | NP_001353314.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000527 AC: 12AN: 227574 AF XY: 0.0000809 show subpopulations
GnomAD4 exome AF: 0.0000250 AC: 36AN: 1438262Hom.: 0 Cov.: 31 AF XY: 0.0000294 AC XY: 21AN XY: 715004 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74370 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CARD14 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 565760). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. This variant is present in population databases (rs772988369, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 260 of the CARD14 protein (p.Gly260Arg). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at