rs9610775

chr22-37510255-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3179 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25922 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.08

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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	UniProt
CARD10	NM_014550.4	c.866G>A	p.Arg289Gln	missense_variant	4/20	ENST00000251973.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD10	ENST00000251973.10	c.866G>A	p.Arg289Gln	missense_variant	4/20	1	NM_014550.4	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30446 AN: 151858 Hom.: 3177 Cov.: 32

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

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.: 37 AF XY: 0.188 AC XY: 135884 AN XY: 722378

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.: 32 AF XY: 0.201 AC XY: 14967 AN XY: 74330

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: criteria provided, single submitter

Submissions by phenotype

CARD10-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.50
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.80	P;P
PrimateAI	Benign	0.40	T
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	T
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

Other links and lift over

dbSNP: rs9610775; hg19: chr22-37906262; COSMIC: COSV52655956; COSMIC: COSV52655956;