chr22-37495950-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014550.4(CARD10):c.2113G>A(p.Glu705Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00165 in 1,614,122 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00096 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 36 hom. )
Consequence
CARD10
NM_014550.4 missense
NM_014550.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 3.83
Genes affected
CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0066081583).
BP6
Variant 22-37495950-C-T is Benign according to our data. Variant chr22-37495950-C-T is described in ClinVar as [Benign]. Clinvar id is 3043839.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000965 (147/152340) while in subpopulation SAS AF= 0.0267 (129/4828). AF 95% confidence interval is 0.023. There are 1 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 36 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD10 | NM_014550.4 | c.2113G>A | p.Glu705Lys | missense_variant | 14/20 | ENST00000251973.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD10 | ENST00000251973.10 | c.2113G>A | p.Glu705Lys | missense_variant | 14/20 | 1 | NM_014550.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000972 AC: 148AN: 152222Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00367 AC: 923AN: 251196Hom.: 15 AF XY: 0.00487 AC XY: 661AN XY: 135856
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GnomAD4 exome AF: 0.00172 AC: 2509AN: 1461782Hom.: 36 Cov.: 33 AF XY: 0.00246 AC XY: 1787AN XY: 727194
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GnomAD4 genome AF: 0.000965 AC: 147AN: 152340Hom.: 1 Cov.: 33 AF XY: 0.00130 AC XY: 97AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CARD10-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 07, 2019 | This variant is classified as 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;N;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;T
Sift4G
Uncertain
D;T;D;.;.
Polyphen
P;.;P;.;.
Vest4
MVP
MPC
ClinPred
T
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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