7-2937133-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032415.7(CARD11):ā€‹c.1245C>Gā€‹(p.Asp415Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CARD11
NM_032415.7 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.431
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARD11NM_032415.7 linkc.1245C>G p.Asp415Glu missense_variant 9/25 ENST00000396946.9 NP_115791.3 Q9BXL7A0A024R854Q8TES3
CARD11NM_001324281.3 linkc.1245C>G p.Asp415Glu missense_variant 10/26 NP_001311210.1 Q9BXL7A0A024R854Q8TES3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARD11ENST00000396946.9 linkc.1245C>G p.Asp415Glu missense_variant 9/251 NM_032415.7 ENSP00000380150.4 Q9BXL7
CARD11ENST00000698637.1 linkn.1571C>G non_coding_transcript_exon_variant 9/24
CARD11ENST00000698654.1 linkn.1504C>G non_coding_transcript_exon_variant 9/10
CARD11ENST00000698662.1 linkn.1445C>G non_coding_transcript_exon_variant 9/10

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251382
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461874
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.74
D
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.37
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.13
Sift
Benign
0.30
T
Sift4G
Uncertain
0.0060
D
Polyphen
0.89
P
Vest4
0.69
MutPred
0.20
Gain of methylation at K413 (P = 0.1645);
MVP
0.35
MPC
1.3
ClinPred
0.95
D
GERP RS
-0.61
Varity_R
0.32
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6945582; hg19: chr7-2976767; API