17-80184099-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBS1_SupportingBS2_Supporting
The NM_001366385.1(CARD14):c.536G>A(p.Arg179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,580,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.536G>A | p.Arg179His | missense_variant | Exon 7 of 24 | ENST00000648509.2 | NP_001353314.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000187 AC: 36AN: 192486Hom.: 0 AF XY: 0.000213 AC XY: 22AN XY: 103438
GnomAD4 exome AF: 0.000299 AC: 427AN: 1428190Hom.: 0 Cov.: 31 AF XY: 0.000298 AC XY: 211AN XY: 707316
GnomAD4 genome AF: 0.000250 AC: 38AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74376
ClinVar
Submissions by phenotype
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:2
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 179 of the CARD14 protein (p.Arg179His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with psoriasis (PMID: 22521419, 25989471, 28887889). ClinVar contains an entry for this variant (Variation ID: 68783). 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 are conflicting or provide insufficient evidence to determine the effect of this variant on CARD14 function (PMID: 22521419). 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. -
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not provided Uncertain:1Other:1
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BP4 -
Autoinflammatory syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at