rs117016854
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_032415.7(CARD11):c.180G>T(p.Val60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00090 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 0 hom. )
Consequence
CARD11
NM_032415.7 synonymous
NM_032415.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.290
Genes affected
CARD11 (HGNC:16393): (caspase recruitment domain family member 11) The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
Variant 7-2947615-C-A is Benign according to our data. Variant chr7-2947615-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 540983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.29 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0009 (137/152276) while in subpopulation AMR AF= 0.00334 (51/15288). AF 95% confidence interval is 0.00261. There are 1 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD11 | NM_032415.7 | c.180G>T | p.Val60= | synonymous_variant | 3/25 | ENST00000396946.9 | |
CARD11 | NM_001324281.3 | c.180G>T | p.Val60= | synonymous_variant | 4/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD11 | ENST00000396946.9 | c.180G>T | p.Val60= | synonymous_variant | 3/25 | 1 | NM_032415.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000907 AC: 138AN: 152158Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000891 AC: 224AN: 251472Hom.: 0 AF XY: 0.000824 AC XY: 112AN XY: 135910
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GnomAD4 exome AF: 0.00103 AC: 1502AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.000987 AC XY: 718AN XY: 727236
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GnomAD4 genome ? AF: 0.000900 AC: 137AN: 152276Hom.: 1 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 08, 2022 | - - |
Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 30, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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