Variant 11-105138979-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.107G>T(p.Ser36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

CARD18
NM_021571.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.16

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=0.18659678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD18	NM_021571.4 linkuse as main transcript	c.107G>T	p.Ser36Ile	missense_variant	2/3	ENST00000530950.2	NP_067546.1	P57730

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CARD18	ENST00000530950.2 linkuse as main transcript	c.107G>T	p.Ser36Ile	missense_variant	2/3	5	NM_021571.4	ENSP00000436691.1	P57730
CARD18	ENST00000526823.1 linkuse as main transcript	c.-11G>T		5_prime_UTR_variant	1/2	1		ENSP00000437035.1	G5EA35
CARD18	ENST00000532895.1 linkuse as main transcript	c.-11G>T		5_prime_UTR_variant	2/3	2		ENSP00000437187.1	G5EA35
CARD18	ENST00000649856.1 linkuse as main transcript	c.-11G>T		5_prime_UTR_variant	7/8			ENSP00000497940.1	G5EA35

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000644

AC:

AN:

248384

Hom.:

AF XY:

0.0000816

AC XY:

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461444

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 06, 2021

The c.107G>T (p.S36I) 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 107, causing the serine (S) at amino acid position 36 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.74

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.70

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.32

M_CAP

Benign

0.0066

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.098

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.99

Vest4

0.16

MutPred

0.59

Loss of disorder (P = 0.0258);

MVP

0.17

MPC

0.19

ClinPred

0.34

GERP RS

-4.0

Varity_R

0.33

gMVP

0.16

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