Variant 11-105138926-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021571.4(CARD18):c.160G>T(p.Ala54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,613,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 1 hom. )

Consequence

CARD18
NM_021571.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

CARD18 (HGNC:28861): (caspase recruitment domain family member 18) Enables CARD domain binding activity and caspase binding activity. Involved in inhibition of cysteine-type endopeptidase activity; negative regulation of interleukin-1 beta production; and negative regulation of protein binding activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CARD18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13934338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD18	NM_021571.4 linkuse as main transcript	c.160G>T	p.Ala54Ser	missense_variant	2/3	ENST00000530950.2	NP_067546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CARD18	ENST00000530950.2 linkuse as main transcript	c.160G>T	p.Ala54Ser	missense_variant	2/3	5	NM_021571.4	ENSP00000436691	P1
CARD18	ENST00000526823.1 linkuse as main transcript	c.43G>T	p.Ala15Ser	missense_variant	1/2	1		ENSP00000437035
CARD18	ENST00000532895.1 linkuse as main transcript	c.43G>T	p.Ala15Ser	missense_variant	2/3	2		ENSP00000437187
CARD18	ENST00000649856.1 linkuse as main transcript	c.43G>T	p.Ala15Ser	missense_variant	7/8			ENSP00000497940

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000466

AC:

116

AN:

248766

Hom.:

AF XY:

0.000422

AC XY:

AN XY:

134930

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000650

Gnomad NFE exome

AF:

0.000870

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000836

AC:

1222

AN:

1461514

Hom.:

Cov.:

AF XY:

0.000796

AC XY:

579

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000493

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000709

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000725

AC:

ExAC

AF:

0.000480

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.00136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.160G>T (p.A54S) alteration is located in exon 2 (coding exon 2) of the CARD18 gene. This alteration results from a G to T substitution at nucleotide position 160, causing the alanine (A) at amino acid position 54 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.

Eigen

Benign

-0.087

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

T;.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.7

D;.;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0090

D;.;D;D

Sift4G

Pathogenic

0.0

D;.;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.47

MVP

0.081

MPC

0.25

ClinPred

0.12

GERP RS

1.8

Varity_R

0.16

gMVP

0.091

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