2-102424325-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001393487.1(IL18RAP):c.490G>T(p.Asp164Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

IL18RAP
NM_001393487.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.69

Variant links:

Genes affected

IL18RAP (HGNC:5989): (interleukin 18 receptor accessory protein) The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn's disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

IL18RAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004480034).

BP6

Variant 2-102424325-G-T is Benign according to our data. Variant chr2-102424325-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2255436.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1 linkuse as main transcript	c.490G>T	p.Asp164Tyr	missense_variant	3/10	ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1 linkuse as main transcript	c.490G>T	p.Asp164Tyr	missense_variant	3/10		NM_001393487.1	P1	O95256-1
IL18RAP	ENST00000264260.6 linkuse as main transcript	c.490G>T	p.Asp164Tyr	missense_variant	5/12	1		P1	O95256-1
IL18RAP	ENST00000409369.1 linkuse as main transcript	c.64G>T	p.Asp22Tyr	missense_variant	3/10	1			O95256-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000278

AC:

AN:

248336

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

134378

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000168

AC:

245

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000674

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000125

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

Cadd

Benign

0.010

Dann

Benign

0.13

DEOGEN2

Benign

0.080

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.9

N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.10

MVP

0.37

MPC

0.21

ClinPred

0.026

GERP RS

-9.9

Varity_R

0.055

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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