Genetic Variant IL18R1:c.*404G>C (chr2-102397290-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003855.5(IL18R1):c.*404G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 161,906 control chromosomes in the GnomAD database, including 4,177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4049 hom., cov: 32)

Exomes 𝑓: 0.15 ( 128 hom. )

Consequence

IL18R1
NM_003855.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.692

Publications

17 publications found

Variant links:

Genes affected

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

IL18R1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5 link	c.*404G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
IL18R1	ENST00000233957.7 link	c.*404G>C	3_prime_UTR_variant	Exon 11 of 11	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000677287.1 link	n.*1574G>C	non_coding_transcript_exon_variant	Exon 11 of 11			ENSP00000503023.1
IL18R1	ENST00000409599.5 link	c.*404G>C	3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000387211.1
IL18R1	ENST00000677287.1 link	n.*1574G>C	3_prime_UTR_variant	Exon 11 of 11			ENSP00000503023.1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32908

AN:

152020

Hom.:

4047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.0949

Gnomad SAS

AF:

0.0746

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.146

AC:

1430

AN:

9768

Hom.:

128

Cov.:

AF XY:

0.144

AC XY:

755

AN XY:

5236

show subpopulations

African (AFR)

AF:

0.256

AC:

AN:

160

American (AMR)

AF:

0.119

AC:

104

AN:

876

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

AN:

192

East Asian (EAS)

AF:

0.120

AC:

AN:

418

South Asian (SAS)

AF:

0.0548

AC:

AN:

748

European-Finnish (FIN)

AF:

0.139

AC:

AN:

294

Middle Eastern (MID)

AF:

0.0417

AC:

AN:

European-Non Finnish (NFE)

AF:

0.158

AC:

1037

AN:

6552

Other (OTH)

AF:

0.129

AC:

AN:

504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

128

191

255

319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.217

AC:

32939

AN:

152138

Hom.:

4049

Cov.:

AF XY:

0.213

AC XY:

15844

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.328

AC:

13604

AN:

41498

American (AMR)

AF:

0.170

AC:

2594

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3472

East Asian (EAS)

AF:

0.0951

AC:

492

AN:

5174

South Asian (SAS)

AF:

0.0740

AC:

357

AN:

4822

European-Finnish (FIN)

AF:

0.191

AC:

2017

AN:

10574

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12328

AN:

67986

Other (OTH)

AF:

0.212

AC:

448

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1280

2560

3841

5121

6401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0937

Hom.:

124

Bravo

AF:

0.219

Asia WGS

AF:

0.0930

AC:

324

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.53

(source)

DANN

Benign

0.53

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over