rs74951924
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_001366385.1(CARD14):c.1170C>A(p.Phe390Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. F390F) has been classified as Likely benign.
Frequency
Consequence
NM_001366385.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.1170C>A | p.Phe390Leu | missense_variant | 11/24 | ENST00000648509.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.1170C>A | p.Phe390Leu | missense_variant | 11/24 | NM_001366385.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461484Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727064
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CARD14-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 390 of the CARD14 protein (p.Phe390Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. - |
Autoinflammatory syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 25, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at