dbSNP rs139006752: CARD10:p.Ala328Val (chr22-37508609-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014550.4(CARD10):c.983C>T(p.Ala328Val) variant causes a missense change. The variant allele was found at a frequency of 0.00194 in 1,578,920 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 6.53

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017548949).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD10	NM_014550.4 link	c.983C>T	p.Ala328Val	missense_variant	Exon 5 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.983C>T	p.Ala328Val	missense_variant	Exon 5 of 20	1	NM_014550.4	ENSP00000251973.5		Q9BWT7-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00172

AC:

329

AN:

191068

Hom.:

AF XY:

0.00174

AC XY:

182

AN XY:

104664

show subpopulations

Gnomad AFR exome

AF:

0.000364

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000381

Gnomad FIN exome

AF:

0.000172

Gnomad NFE exome

AF:

0.00244

Gnomad OTH exome

AF:

0.00301

GnomAD4 exome

AF:

0.00200

AC:

2849

AN:

1426620

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1403

AN XY:

707846

show subpopulations

Gnomad4 AFR exome

AF:

0.000455

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000845

Gnomad4 FIN exome

AF:

0.000164

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00144

AC:

220

AN:

152300

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00134

AC:

160

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

Mar 29, 2016

Flinders Ophthalmology, Flinders University

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: case-control

GWAS associated gene CARD10 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.64

D;.;D

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.98

D;.;D

Vest4

0.61

MVP

0.89

MPC

0.83

ClinPred

0.036

GERP RS

5.3

Varity_R

0.47

gMVP

0.74

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