Variant 11-105138998-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021571.4(CARD18):c.88T>A(p.Leu30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

CARD18
NM_021571.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062087685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD18	NM_021571.4 linkuse as main transcript	c.88T>A	p.Leu30Ile	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.88T>A	p.Leu30Ile	missense_variant	2/3	5	NM_021571.4	ENSP00000436691	P1
CARD18	ENST00000526823.1 linkuse as main transcript	c.-30T>A		5_prime_UTR_variant	1/2	1		ENSP00000437035
CARD18	ENST00000532895.1 linkuse as main transcript	c.-30T>A		5_prime_UTR_variant	2/3	2		ENSP00000437187
CARD18	ENST00000649856.1 linkuse as main transcript	c.-30T>A		5_prime_UTR_variant	7/8			ENSP00000497940

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000262

AC:

AN:

248272

Hom.:

AF XY:

0.000201

AC XY:

AN XY:

134618

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000202

AC:

295

AN:

1461416

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000210

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000190

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000296

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

May 04, 2022

The c.88T>A (p.L30I) alteration is located in exon 2 (coding exon 2) of the CARD18 gene. This alteration results from a T to A substitution at nucleotide position 88, causing the leucine (L) at amino acid position 30 to be replaced by an isoleucine (I). 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

-0.57

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.3

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.78

M_CAP

Benign

0.021

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.7

REVEL

Benign

0.020

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.27

MVP

0.14

MPC

0.24

ClinPred

0.043

GERP RS

0.34

Varity_R

0.12

gMVP

0.041

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