rs376630011
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001366385.1(CARD14):c.963+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,593,144 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
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
CARD14
NM_001366385.1 splice_donor_region, intron
NM_001366385.1 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0005645
2
Clinical Significance
Conservation
PhyloP100: -0.563
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.963+6G>A | splice_donor_region_variant, intron_variant | ENST00000648509.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.963+6G>A | splice_donor_region_variant, intron_variant | NM_001366385.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000221 AC: 5AN: 226112Hom.: 0 AF XY: 0.0000322 AC XY: 4AN XY: 124234
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GnomAD4 exome AF: 0.0000264 AC: 38AN: 1440994Hom.: 0 Cov.: 31 AF XY: 0.0000251 AC XY: 18AN XY: 717166
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change falls in intron 6 of the CARD14 gene. It does not directly change the encoded amino acid sequence of the CARD14 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs376630011, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. ClinVar contains an entry for this variant (Variation ID: 574789). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at