rs147422861
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_032415.7(CARD11):c.3454G>A(p.Asp1152Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000419 in 1,613,378 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 2 hom. )
Consequence
CARD11
NM_032415.7 missense
NM_032415.7 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 7.20
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CARD11
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0068109334).
BP6
?
Variant 7-2906649-C-T is Benign according to our data. Variant chr7-2906649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133803.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 = 0.00201 (306/152388) while in subpopulation AFR AF= 0.00683 (284/41594). AF 95% confidence interval is 0.00618. There are 2 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 33. 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.3454G>A | p.Asp1152Asn | missense_variant | 25/25 | ENST00000396946.9 | |
CARD11 | NM_001324281.3 | c.3454G>A | p.Asp1152Asn | missense_variant | 26/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD11 | ENST00000396946.9 | c.3454G>A | p.Asp1152Asn | missense_variant | 25/25 | 1 | NM_032415.7 | P1 | |
CARD11 | ENST00000698637.1 | n.4564G>A | non_coding_transcript_exon_variant | 24/24 | |||||
CARD11 | ENST00000698652.1 | n.2410G>A | non_coding_transcript_exon_variant | 8/8 |
Frequencies
GnomAD3 genomes ? AF: 0.00201 AC: 306AN: 152270Hom.: 2 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
306
AN:
152270
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000579 AC: 145AN: 250454Hom.: 1 AF XY: 0.000413 AC XY: 56AN XY: 135440
GnomAD3 exomes
AF:
AC:
145
AN:
250454
Hom.:
AF XY:
AC XY:
56
AN XY:
135440
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000253 AC: 370AN: 1460990Hom.: 2 Cov.: 30 AF XY: 0.000217 AC XY: 158AN XY: 726686
GnomAD4 exome
AF:
AC:
370
AN:
1460990
Hom.:
Cov.:
30
AF XY:
AC XY:
158
AN XY:
726686
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00201 AC: 306AN: 152388Hom.: 2 Cov.: 33 AF XY: 0.00180 AC XY: 134AN XY: 74512
GnomAD4 genome
?
AF:
AC:
306
AN:
152388
Hom.:
Cov.:
33
AF XY:
AC XY:
134
AN XY:
74512
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
32
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
91
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Severe combined immunodeficiency due to CARD11 deficiency;C4539957:Immunodeficiency 11b with atopic dermatitis;C4551967:BENTA disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 18, 2022 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at