rs34632751

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001184900.3(CARD8):c.1385A>G(p.Gln462Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,614,094 control chromosomes in the GnomAD database, including 547 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 26 hom., cov: 32)

Exomes 𝑓: 0.024 ( 521 hom. )

Consequence

CARD8
NM_001184900.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.216

Publications

10 publications found

Variant links:

Genes affected

CARD8 (HGNC:17057): (caspase recruitment domain family member 8) The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB). This protein may be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. It is thought that this protein acts as an adaptor molecule that negatively regulates NFKB activation, CASP1-dependent IL1B secretion, and apoptosis. Polymorphisms in this gene may be associated with a susceptibility to rheumatoid arthritis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

CARD8 Gene-Disease associations (from GenCC):

inflammatory bowel disease 30
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CARD8 links:

ENSG00000268583 (HGNC:):

ENSG00000268583 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034770072).

BP6

Variant 19-48211939-T-C is Benign according to our data. Variant chr19-48211939-T-C is described in ClinVar as [Benign]. Clinvar id is 1169236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0181 (2763/152278) while in subpopulation NFE AF = 0.0282 (1917/68018). AF 95% confidence interval is 0.0271. There are 26 homozygotes in GnomAd4. There are 1326 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD8	NM_001184900.3 link	c.1385A>G	p.Gln462Arg	missense_variant	Exon 14 of 14	ENST00000651546.1	NP_001171829.1	Q9Y2G2-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1 link	c.1385A>G	p.Gln462Arg	missense_variant	Exon 14 of 14		NM_001184900.3	ENSP00000499211.1		Q9Y2G2-5

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2763

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0282

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0198

AC:

4962

AN:

250060

AF XY:

0.0198

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0384

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0243

AC:

35483

AN:

1461816

Hom.:

521

Cov.:

AF XY:

0.0236

AC XY:

17140

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00376

AC:

126

AN:

33480

American (AMR)

AF:

0.0124

AC:

556

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00983

AC:

257

AN:

26134

East Asian (EAS)

AF:

0.000151

AC:

AN:

39692

South Asian (SAS)

AF:

0.00128

AC:

110

AN:

86252

European-Finnish (FIN)

AF:

0.0396

AC:

2118

AN:

53420

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0280

AC:

31137

AN:

1111952

Other (OTH)

AF:

0.0192

AC:

1157

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1798

3596

5394

7192

8990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0181

AC:

2763

AN:

152278

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1326

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00448

AC:

186

AN:

41560

American (AMR)

AF:

0.0132

AC:

202

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0353

AC:

375

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0282

AC:

1917

AN:

68018

Other (OTH)

AF:

0.0104

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

259

389

518

648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.0245

AC:

ALSPAC

AF:

0.0246

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0252

AC:

217

ExAC

AF:

0.0204

AC:

2482

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0254

EpiControl

AF:

0.0248

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.8

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.52

T;T;.;.;.

MetaRNN

Benign

0.0035

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

0.22

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.037

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Vest4

0.090

MPC

0.20

ClinPred

0.0093

GERP RS

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs34632751

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