Variant rs9610775 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014550.4(CARD10):c.866G>A(p.Arg289Gln) variant causes a missense change. The variant allele was found at a frequency of 0.188 in 1,603,122 control chromosomes in the GnomAD database, including 29,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3179 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25922 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.08

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002108544).

BP6

Variant 22-37510255-C-T is Benign according to our data. Variant chr22-37510255-C-T is described in ClinVar as [Benign]. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD10	NM_014550.4 link	c.866G>A	p.Arg289Gln	missense_variant	4/20	ENST00000251973.10	NP_055365.2	Q9BWT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10 link	c.866G>A	p.Arg289Gln	missense_variant	4/20	1	NM_014550.4	ENSP00000251973.5		Q9BWT7-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30446

AN:

151858

Hom.:

3177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.183

AC:

43767

AN:

239630

Hom.:

4314

AF XY:

0.189

AC XY:

24666

AN XY:

130736

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.186

AC:

270129

AN:

1451148

Hom.:

25922

Cov.:

AF XY:

0.188

AC XY:

135884

AN XY:

722378

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.200

AC:

30470

AN:

151974

Hom.:

3179

Cov.:

AF XY:

0.201

AC XY:

14967

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.180

Hom.:

2335

Bravo

AF:

0.196

TwinsUK

AF:

0.192

AC:

711

ALSPAC

AF:

0.180

AC:

693

ESP6500AA

AF:

0.239

AC:

1053

ESP6500EA

AF:

0.181

AC:

1557

ExAC

AF:

0.185

AC:

22482

Asia WGS

AF:

0.210

AC:

732

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CARD10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;D

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.10

Sift

Benign

0.16

T;T

Sift4G

Benign

0.14

T;T

Polyphen

1.0

D;D

Vest4

0.22

MPC

0.57

ClinPred

0.013

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.36

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