22-37491768-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014550.4(CARD10):​c.2851G>A​(p.Val951Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,569,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 26)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125
Variant links:
Genes affected
CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03396955).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARD10NM_014550.4 linkc.2851G>A p.Val951Ile missense_variant Exon 19 of 20 ENST00000251973.10 NP_055365.2 Q9BWT7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARD10ENST00000251973.10 linkc.2851G>A p.Val951Ile missense_variant Exon 19 of 20 1 NM_014550.4 ENSP00000251973.5 Q9BWT7-1

Frequencies

GnomAD3 genomes
AF:
0.0000547
AC:
8
AN:
146192
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.0000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000903
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000803
AC:
20
AN:
248988
Hom.:
0
AF XY:
0.0000667
AC XY:
9
AN XY:
134998
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:
0.000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000164
AC:
233
AN:
1423720
Hom.:
0
Cov.:
28
AF XY:
0.000169
AC XY:
120
AN XY:
709664
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:
0.000213
Gnomad4 OTH exome
AF:
0.0000510
GnomAD4 genome
AF:
0.0000547
AC:
8
AN:
146192
Hom.:
0
Cov.:
26
AF XY:
0.0000563
AC XY:
4
AN XY:
71052
show subpopulations
Gnomad4 AFR
AF:
0.0000507
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000903
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000121
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000357

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2851G>A (p.V951I) alteration is located in exon 19 (coding exon 19) of the CARD10 gene. This alteration results from a G to A substitution at nucleotide position 2851, causing the valine (V) at amino acid position 951 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.29
DEOGEN2
Benign
0.073
T;.;T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.78
.;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.034
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.54
N;.;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
0.020
N;N;N
REVEL
Benign
0.025
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0010
B;.;B
Vest4
0.28
MVP
0.24
MPC
0.26
ClinPred
0.027
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.031
gMVP
0.23

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: rs570147231; hg19: chr22-37887775; API