Genetic Variant IL18R1:c.*968C>A (chr2-102397854-C-A) – 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.*968C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,230 control chromosomes in the GnomAD database, including 538 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 0.075 ( 538 hom., cov: 32)

Exomes 𝑓: 0.098 ( 0 hom. )

Consequence

IL18R1
NM_003855.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.02

Publications

5 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18R1	NM_003855.5	MANE Select	c.*968C>A	3_prime_UTR	Exon 11 of 11	NP_003846.1
IL18R1	NM_001371418.1		c.*968C>A	3_prime_UTR	Exon 11 of 11	NP_001358347.1
IL18R1	NM_001371421.1		c.*968C>A	3_prime_UTR	Exon 13 of 13	NP_001358350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.*968C>A	3_prime_UTR	Exon 11 of 11	ENSP00000233957.1
IL18R1	ENST00000677287.1		n.*2138C>A	non_coding_transcript_exon	Exon 11 of 11	ENSP00000503023.1
IL18R1	ENST00000409599.5	TSL:5	c.*968C>A	3_prime_UTR	Exon 12 of 12	ENSP00000387211.1

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

11418

AN:

152032

Hom.:

538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0725

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0409

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.0976

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0800

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.118

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0751

AC:

11420

AN:

152148

Hom.:

538

Cov.:

AF XY:

0.0754

AC XY:

5605

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0406

AC:

1685

AN:

41504

American (AMR)

AF:

0.0724

AC:

1107

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3470

East Asian (EAS)

AF:

0.0408

AC:

211

AN:

5174

South Asian (SAS)

AF:

0.0824

AC:

397

AN:

4818

European-Finnish (FIN)

AF:

0.107

AC:

1131

AN:

10572

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0870

AC:

5917

AN:

67996

Other (OTH)

AF:

0.102

AC:

216

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

527

1053

1580

2106

2633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0382

Hom.:

Bravo

AF:

0.0705

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.081

(source)

DANN

Benign

0.75

PhyloP100

-3.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over