rs115582620
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001366385.1(CARD14):c.185G>A(p.Arg62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,552,610 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00085 ( 12 hom. )
Consequence
CARD14
NM_001366385.1 missense
NM_001366385.1 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 1.32
Genes affected
CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0036271214).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00423 (644/152316) while in subpopulation AFR AF= 0.0143 (596/41564). AF 95% confidence interval is 0.0134. There are 4 homozygotes in gnomad4. There are 301 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 644 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.185G>A | p.Arg62Gln | missense_variant | 5/24 | ENST00000648509.2 | NP_001353314.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.185G>A | p.Arg62Gln | missense_variant | 5/24 | NM_001366385.1 | ENSP00000498071 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00417 AC: 635AN: 152198Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00138 AC: 212AN: 153392Hom.: 0 AF XY: 0.00101 AC XY: 82AN XY: 81550
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GnomAD4 exome AF: 0.000851 AC: 1191AN: 1400294Hom.: 12 Cov.: 32 AF XY: 0.000763 AC XY: 527AN XY: 691092
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GnomAD4 genome AF: 0.00423 AC: 644AN: 152316Hom.: 4 Cov.: 33 AF XY: 0.00404 AC XY: 301AN XY: 74488
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ESP6500AA
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | CARD14: BP4, BS1, BS2 - |
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 01, 2021 | - - |
CARD14-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 15, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;.;.;.;N
REVEL
Benign
Sift
Benign
.;.;.;.;T
Sift4G
Benign
T;.;T;T;T
Polyphen
B;B;.;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at