Genetic Variant IL18R1:c.*46delG (chr2-102396928-TG-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_003855.5(IL18R1):c.*46delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,242,206 control chromosomes in the GnomAD database, including 714 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 49 hom., cov: 32)

Exomes 𝑓: 0.031 ( 665 hom. )

Consequence

IL18R1
NM_003855.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0243 (3706/152304) while in subpopulation NFE AF = 0.0373 (2534/68026). AF 95% confidence interval is 0.036. There are 49 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5 link	c.*46delG		3_prime_UTR_variant	Exon 11 of 11	ENST00000233957.7	NP_003846.1	Q13478

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7 link	c.*46delG		3_prime_UTR_variant	Exon 11 of 11	5	NM_003855.5	ENSP00000233957.1		Q13478

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3708

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00680

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0372

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.0273

AC:

4533

AN:

166066

AF XY:

0.0285

show subpopulations

Gnomad AFR exome

AF:

0.00683

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.000475

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0314

AC:

34217

AN:

1089902

Hom.:

665

Cov.:

AF XY:

0.0318

AC XY:

17503

AN XY:

549648

show subpopulations

Gnomad4 AFR exome

AF:

0.00505

AC:

126

AN:

24960

Gnomad4 AMR exome

AF:

0.0186

AC:

537

AN:

28922

Gnomad4 ASJ exome

AF:

0.00483

AC:

AN:

18850

Gnomad4 EAS exome

AF:

0.000899

AC:

AN:

37834

Gnomad4 SAS exome

AF:

0.0381

AC:

2483

AN:

65170

Gnomad4 FIN exome

AF:

0.0375

AC:

1868

AN:

49862

Gnomad4 NFE exome

AF:

0.0341

AC:

27715

AN:

812102

Gnomad4 Remaining exome

AF:

0.0268

AC:

1270

AN:

47374

Heterozygous variant carriers

1691

3382

5072

6763

8454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.0243

AC:

3706

AN:

152304

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1846

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00678

AC:

0.00678309

AN:

0.00678309

Gnomad4 AMR

AF:

0.0139

AC:

0.0138598

AN:

0.0138598

Gnomad4 ASJ

AF:

0.00403

AC:

0.00403458

AN:

0.00403458

Gnomad4 EAS

AF:

0.000965

AC:

0.000964878

AN:

0.000964878

Gnomad4 SAS

AF:

0.0342

AC:

0.0341898

AN:

0.0341898

Gnomad4 FIN

AF:

0.0407

AC:

0.040724

AN:

0.040724

Gnomad4 NFE

AF:

0.0373

AC:

0.0372505

AN:

0.0372505

Gnomad4 OTH

AF:

0.0213

AC:

0.0212665

AN:

0.0212665

Heterozygous variant carriers

195

389

584

778

973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0293

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over