NM_001184900.3:c.1549C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001184900.3(CARD8):​c.1549C>T​(p.Leu517Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L517V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CARD8
NM_001184900.3 missense

Scores

1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457
Variant links:
Genes affected
CARD8 (HGNC:17057): (caspase recruitment domain family member 8) The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB). This protein may be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. It is thought that this protein acts as an adaptor molecule that negatively regulates NFKB activation, CASP1-dependent IL1B secretion, and apoptosis. Polymorphisms in this gene may be associated with a susceptibility to rheumatoid arthritis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10658112).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARD8NM_001184900.3 linkc.1549C>T p.Leu517Phe missense_variant Exon 14 of 14 ENST00000651546.1 NP_001171829.1 Q9Y2G2-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARD8ENST00000651546.1 linkc.1549C>T p.Leu517Phe missense_variant Exon 14 of 14 NM_001184900.3 ENSP00000499211.1 Q9Y2G2-5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461862
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
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:
0.00000180
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
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
11
DANN
Benign
0.94
Eigen
Benign
-0.87
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0064
N
LIST_S2
Benign
0.46
T;T;.;.;.
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.36
N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.53
T;T;T;T;T
Sift4G
Pathogenic
0.0
D;D;D;D;D
Vest4
0.22
MVP
0.048
MPC
0.21
ClinPred
0.088
T
GERP RS
-1.6

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48715032; API