rs146678380
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001366385.1(CARD14):c.2569+4T>C 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 0.00258 in 1,608,286 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 8 hom. )
Consequence
CARD14
NM_001366385.1 splice_donor_region, intron
NM_001366385.1 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00007751
2
Clinical Significance
Conservation
PhyloP100: -3.84
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-80205209-T-C is Benign according to our data. Variant chr17-80205209-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 527886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80205209-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00184 (280/152234) while in subpopulation NFE AF= 0.00325 (221/67986). AF 95% confidence interval is 0.0029. There are 2 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 280 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.2569+4T>C | splice_donor_region_variant, intron_variant | ENST00000648509.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.2569+4T>C | splice_donor_region_variant, intron_variant | NM_001366385.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00184 AC: 280AN: 152116Hom.: 2 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00176 AC: 435AN: 246506Hom.: 2 AF XY: 0.00196 AC XY: 262AN XY: 133412
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GnomAD4 exome AF: 0.00266 AC: 3876AN: 1456052Hom.: 8 Cov.: 35 AF XY: 0.00266 AC XY: 1924AN XY: 723682
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GnomAD4 genome ? AF: 0.00184 AC: 280AN: 152234Hom.: 2 Cov.: 32 AF XY: 0.00165 AC XY: 123AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | CARD14: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 20, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at