rs35692270
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001366385.1(CARD14):c.2193G>A(p.Ala731=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,612,880 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0081 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 14 hom. )
Consequence
CARD14
NM_001366385.1 synonymous
NM_001366385.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.198
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-80202394-G-A is Benign according to our data. Variant chr17-80202394-G-A is described in ClinVar as [Benign]. Clinvar id is 458094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.198 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00813 (1238/152208) while in subpopulation AFR AF= 0.0283 (1176/41534). AF 95% confidence interval is 0.027. There are 19 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1231 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.2193G>A | p.Ala731= | synonymous_variant | 18/24 | ENST00000648509.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.2193G>A | p.Ala731= | synonymous_variant | 18/24 | NM_001366385.1 | P1 | ||
ENST00000570309.1 | n.2678C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.00809 AC: 1231AN: 152090Hom.: 19 Cov.: 32
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GnomAD3 exomes AF: 0.00224 AC: 558AN: 249526Hom.: 9 AF XY: 0.00169 AC XY: 229AN XY: 135276
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GnomAD4 exome AF: 0.000905 AC: 1322AN: 1460672Hom.: 14 Cov.: 32 AF XY: 0.000795 AC XY: 578AN XY: 726642
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GnomAD4 genome ? AF: 0.00813 AC: 1238AN: 152208Hom.: 19 Cov.: 32 AF XY: 0.00762 AC XY: 567AN XY: 74398
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 17, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at