Variant rs200148764 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014550.4(CARD10):c.1024G>A(p.Val342Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,597,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.53

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]

CARD10 links:

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=0.014269799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD10	NM_014550.4 linkuse as main transcript	c.1024G>A	p.Val342Met	missense_variant	5/20	ENST00000251973.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD10	ENST00000251973.10 linkuse as main transcript	c.1024G>A	p.Val342Met	missense_variant	5/20	1	NM_014550.4	P1	Q9BWT7-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

225842

Hom.:

AF XY:

0.000234

AC XY:

AN XY:

123746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00203

Gnomad SAS exome

AF:

0.000346

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000189

AC:

273

AN:

1445288

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

117

AN XY:

718952

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00114

Gnomad4 SAS exome

AF:

0.000271

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000203

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000240

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Primary open angle glaucoma

Other:1

risk factor, no assertion criteria provided

case-control

Flinders Ophthalmology, Flinders University

Mar 29, 2016

GWAS associated gene CARD10 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;T

Eigen

Benign

-0.072

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.036

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.4

L;.;L

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.25

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.038

D;D;D

Sift4G

Benign

0.16

T;D;T

Polyphen

0.037

B;.;B

Vest4

0.72

MutPred

0.32

Gain of disorder (P = 0.0249);.;Gain of disorder (P = 0.0249);

MVP

0.74

MPC

0.34

ClinPred

0.055

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over