rs11881179

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001184900.3(CARD8):c.517A>G(p.Ile173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,608,068 control chromosomes in the GnomAD database, including 726 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 391 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 335 hom. )

Consequence

CARD8
NM_001184900.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.148

Publications

14 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:

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=0.0034451187).

BP6

Variant 19-48231685-T-C is Benign according to our data. Variant chr19-48231685-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184900.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CARD8	NM_001184900.3	MANE Select	c.517A>G	p.Ile173Val	missense	Exon 8 of 14	NP_001171829.1
CARD8	NM_001351782.2		c.517A>G	p.Ile173Val	missense	Exon 9 of 15	NP_001338711.1
CARD8	NM_001184901.1		c.367A>G	p.Ile123Val	missense	Exon 5 of 11	NP_001171830.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CARD8	ENST00000651546.1	MANE Select	c.517A>G	p.Ile173Val	missense	Exon 8 of 14	ENSP00000499211.1
CARD8	ENST00000391898.7	TSL:1	c.517A>G	p.Ile173Val	missense	Exon 5 of 11	ENSP00000375767.3
CARD8	ENST00000520153.5	TSL:1	c.367A>G	p.Ile123Val	missense	Exon 6 of 12	ENSP00000428736.1

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6074

AN:

152112

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.0626

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0130

AC:

3216

AN:

247138

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.00941

Gnomad ASJ exome

AF:

0.00731

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00211

Gnomad OTH exome

AF:

0.00967

GnomAD4 exome

AF:

0.00571

AC:

8314

AN:

1455838

Hom.:

335

Cov.:

AF XY:

0.00548

AC XY:

3969

AN XY:

724030

show subpopulations

African (AFR)

AF:

0.130

AC:

4292

AN:

33060

American (AMR)

AF:

0.0109

AC:

475

AN:

43626

Ashkenazi Jewish (ASJ)

AF:

0.00784

AC:

202

AN:

25768

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39632

South Asian (SAS)

AF:

0.0108

AC:

925

AN:

85460

European-Finnish (FIN)

AF:

0.0000940

AC:

AN:

53176

Middle Eastern (MID)

AF:

0.0157

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00147

AC:

1629

AN:

1109348

Other (OTH)

AF:

0.0116

AC:

695

AN:

60040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

382

764

1145

1527

1909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.0399

AC:

6075

AN:

152230

Hom.:

391

Cov.:

AF XY:

0.0395

AC XY:

2943

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.130

AC:

5417

AN:

41516

American (AMR)

AF:

0.0197

AC:

301

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00196

AC:

133

AN:

68018

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

275

549

824

1098

1373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0148

Hom.:

403

Bravo

AF:

0.0458

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.126

AC:

556

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.0150

AC:

1823

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.34

(source)

DANN

Benign

0.24

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.99

PhyloP100

0.15

PrimateAI

Benign

0.36

PROVEAN

Benign

0.37

REVEL

Benign

0.014

Sift

Benign

0.57

Sift4G

Benign

0.094

Polyphen

0.36

Vest4

0.043

MPC

0.14

ClinPred

0.00037

GERP RS

0.53

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over