rs112606562
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032415.7(CARD11):c.3144+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 1,613,974 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 4 hom. )
Consequence
CARD11
NM_032415.7 intron
NM_032415.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0100
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 7-2912163-C-T is Benign according to our data. Variant chr7-2912163-C-T is described in ClinVar as [Benign]. Clinvar id is 540979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00247 (376/152312) while in subpopulation AFR AF= 0.00844 (351/41572). AF 95% confidence interval is 0.00771. There are 2 homozygotes in gnomad4. There are 173 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD11 | NM_032415.7 | c.3144+9G>A | intron_variant | ENST00000396946.9 | |||
CARD11 | NM_001324281.3 | c.3144+9G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD11 | ENST00000396946.9 | c.3144+9G>A | intron_variant | 1 | NM_032415.7 | P1 | |||
CARD11 | ENST00000698637.1 | n.4254+9G>A | intron_variant, non_coding_transcript_variant | ||||||
CARD11 | ENST00000698652.1 | n.2100+9G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00246 AC: 375AN: 152194Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000654 AC: 164AN: 250682Hom.: 0 AF XY: 0.000427 AC XY: 58AN XY: 135778
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GnomAD4 exome AF: 0.000274 AC: 400AN: 1461662Hom.: 4 Cov.: 31 AF XY: 0.000256 AC XY: 186AN XY: 727130
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GnomAD4 genome ? AF: 0.00247 AC: 376AN: 152312Hom.: 2 Cov.: 32 AF XY: 0.00232 AC XY: 173AN XY: 74488
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ClinVar
Significance: 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 | Dec 14, 2022 | - - |
Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
CARD11-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 02, 2020 | 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
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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