Genetic Variant IL18R1:c.625+152T>C (chr2-102376215-T-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.625+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 502,108 control chromosomes in the GnomAD database, including 145,114 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 0.77 ( 46375 hom., cov: 32)

Exomes 𝑓: 0.74 ( 98739 hom. )

Consequence

IL18R1
NM_003855.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0710

Publications

15 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5 link	c.625+152T>C		intron_variant	Intron 5 of 10	ENST00000233957.7	NP_003846.1	Q13478

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL18R1	ENST00000233957.7 link	c.625+152T>C	intron_variant	Intron 5 of 10	5	NM_003855.5	ENSP00000233957.1	Q13478
IL18R1	ENST00000409599.5 link	c.625+152T>C	intron_variant	Intron 6 of 11	5		ENSP00000387211.1	Q13478
IL18R1	ENST00000410040.5 link	c.625+152T>C	intron_variant	Intron 5 of 10	2		ENSP00000386663.1	Q13478
IL18R1	ENST00000677287.1 link	n.*169+152T>C	intron_variant	Intron 5 of 10			ENSP00000503023.1	Q86YL8

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117405

AN:

152000

Hom.:

46331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.766

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.756

GnomAD4 exome

AF:

0.743

AC:

260206

AN:

349990

Hom.:

98739

AF XY:

0.739

AC XY:

132189

AN XY:

178916

show subpopulations

African (AFR)

AF:

0.892

AC:

7819

AN:

8768

American (AMR)

AF:

0.529

AC:

4277

AN:

8082

Ashkenazi Jewish (ASJ)

AF:

0.766

AC:

7859

AN:

10254

East Asian (EAS)

AF:

0.559

AC:

13385

AN:

23952

South Asian (SAS)

AF:

0.527

AC:

6712

AN:

12744

European-Finnish (FIN)

AF:

0.813

AC:

26615

AN:

32718

Middle Eastern (MID)

AF:

0.736

AC:

1132

AN:

1538

European-Non Finnish (NFE)

AF:

0.766

AC:

177686

AN:

232060

Other (OTH)

AF:

0.741

AC:

14721

AN:

19874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3011

6023

9034

12046

15057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1782

3564

5346

7128

8910

<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:

0.772

AC:

117499

AN:

152118

Hom.:

46375

Cov.:

AF XY:

0.766

AC XY:

56946

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.889

AC:

36870

AN:

41496

American (AMR)

AF:

0.602

AC:

9207

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.766

AC:

2657

AN:

3468

East Asian (EAS)

AF:

0.556

AC:

2871

AN:

5160

South Asian (SAS)

AF:

0.546

AC:

2631

AN:

4820

European-Finnish (FIN)

AF:

0.812

AC:

8573

AN:

10562

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.768

AC:

52251

AN:

68008

Other (OTH)

AF:

0.758

AC:

1603

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1278

2556

3834

5112

6390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.740

Hom.:

9708

Bravo

AF:

0.762

Asia WGS

AF:

0.582

AC:

2025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.49

PhyloP100

0.071

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