Variant rs2043211 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PS1_ModerateBP4_StrongBP6_ModerateBA1

The NM_001184900.3(CARD8):c.304T>A(p.Phe102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,612,308 control chromosomes in the GnomAD database, including 86,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict 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 pathogenicin UniProt.

Frequency

Genomes: 𝑓 0.30 ( 7120 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79001 hom. )

Consequence

CARD8
NM_001184900.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PS1

Transcript NM_001184900.3 (CARD8) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

BP4

Computational evidence support a benign effect (MetaRNN=1.9392371E-4).

BP6

Variant 19-48234449-A-T is Benign according to our data. Variant chr19-48234449-A-T is described in ClinVar as [Benign]. Clinvar id is 1166485.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3 linkuse as main transcript	c.304T>A	p.Phe102Ile	missense_variant	6/14	ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1 linkuse as main transcript	c.304T>A	p.Phe102Ile	missense_variant	6/14		NM_001184900.3	A2	Q9Y2G2-5

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45296

AN:

151914

Hom.:

7119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.327

AC:

82112

AN:

250934

Hom.:

14180

AF XY:

0.331

AC XY:

44923

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.326

AC:

475366

AN:

1460276

Hom.:

79001

Cov.:

AF XY:

0.326

AC XY:

236907

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.325

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.298

AC:

45318

AN:

152032

Hom.:

7120

Cov.:

AF XY:

0.302

AC XY:

22432

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.494

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.309

Alfa

AF:

0.323

Hom.:

6173

Bravo

AF:

0.288

TwinsUK

AF:

0.314

AC:

1164

ALSPAC

AF:

0.312

AC:

1203

ESP6500AA

AF:

0.209

AC:

919

ESP6500EA

AF:

0.329

AC:

2829

ExAC

AF:

0.326

AC:

39622

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.330

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.15

DANN

Benign

0.86

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.46

T;T;.;.;T;.;.

MetaRNN

Benign

0.00019

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

2.1e-9

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

0.070

N;N;N;N;N;N;N

REVEL

Benign

0.025

Sift

Pathogenic

0.0

D;D;.;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

0.66

.;.;P;.;P;.;.

Vest4

0.15

MPC

0.23

ClinPred

0.0052

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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