rs9610775

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R289W) has been classified as Uncertain significance.

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

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 89 and autoimmunity
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CARD10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37510255-C-T is described in CliVar as Benign. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37510255-C-T is described in CliVar as Benign. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37510255-C-T is described in CliVar as Benign. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37510255-C-T is described in CliVar as Benign. Clinvar id is 3060680.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37510255-C-T is described in CliVar 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 rank	MANE	Protein	UniProt
CARD10	NM_014550.4 link	c.866G>A	p.Arg289Gln	missense_variant	Exon 4 of 20	ENST00000251973.10	NP_055365.2	Q9BWT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10 link	c.866G>A	p.Arg289Gln	missense_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.183

AC:

43767

AN:

239630

AF XY:

0.189

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 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

African (AFR)

AF:

0.247

AC:

8270

AN:

33480

American (AMR)

AF:

0.111

AC:

4953

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5732

AN:

26134

East Asian (EAS)

AF:

0.230

AC:

9117

AN:

39694

South Asian (SAS)

AF:

0.240

AC:

20729

AN:

86252

European-Finnish (FIN)

AF:

0.177

AC:

7593

AN:

42886

Middle Eastern (MID)

AF:

0.206

AC:

1189

AN:

5766

European-Non Finnish (NFE)

AF:

0.180

AC:

200568

AN:

1111902

Other (OTH)

AF:

0.199

AC:

11978

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12994

25988

38981

51975

64969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7202

14404

21606

28808

36010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30470

AN:

151974

Hom.:

3179

Cov.:

AF XY:

0.201

AC XY:

14967

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.246

AC:

10214

AN:

41482

American (AMR)

AF:

0.155

AC:

2361

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

729

AN:

3468

East Asian (EAS)

AF:

0.207

AC:

1065

AN:

5150

South Asian (SAS)

AF:

0.249

AC:

1199

AN:

4814

European-Finnish (FIN)

AF:

0.186

AC:

1973

AN:

10582

Middle Eastern (MID)

AF:

0.168

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12307

AN:

67906

Other (OTH)

AF:

0.211

AC:

446

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1229

2458

3687

4916

6145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

3213

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

Nov 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

4.1

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over