Variant rs750643216 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014550.4(CARD10):c.1210C>T(p.Arg404Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,591,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 2.31

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34081316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD10	NM_014550.4 linkuse as main transcript	c.1210C>T	p.Arg404Trp	missense_variant	7/20	ENST00000251973.10	NP_055365.2	Q9BWT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CARD10	ENST00000251973.10 linkuse as main transcript	c.1210C>T	p.Arg404Trp	missense_variant	7/20	1	NM_014550.4	ENSP00000251973.5	Q9BWT7-1
CARD10	ENST00000437756.5 linkuse as main transcript	c.133C>T	p.Arg45Trp	missense_variant	5/15	1		ENSP00000416239.1	B0QYC4
CARD10	ENST00000403299.5 linkuse as main transcript	c.1210C>T	p.Arg404Trp	missense_variant	8/21	5		ENSP00000384570.1	Q9BWT7-1
CARD10	ENST00000406271.7 linkuse as main transcript	c.352C>T	p.Arg118Trp	missense_variant	4/17	2		ENSP00000385799.3	Q9BWT7-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000334

AC:

AN:

239452

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000579

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000208

AC:

AN:

1439106

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

713166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000913

Gnomad4 AMR exome

AF:

0.000163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.0000850

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000819

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

AC:

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

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;.;D;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

.;T;T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Uncertain

0.086

MutationAssessor

Benign

1.6

L;.;L;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;.

Polyphen

0.99

D;.;D;.

Vest4

0.24

MutPred

0.28

Loss of disorder (P = 0.0011);.;Loss of disorder (P = 0.0011);.;

MVP

0.89

MPC

0.73

ClinPred

0.55

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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