Genetic Variant NM_003855.5: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:

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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.

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.*404G>C	3_prime_UTR	Exon 11 of 11	NP_003846.1
IL18R1	NM_001371418.1		c.*404G>C	3_prime_UTR	Exon 11 of 11	NP_001358347.1
IL18R1	NM_001371421.1		c.*404G>C	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.*404G>C	3_prime_UTR	Exon 11 of 11	ENSP00000233957.1
IL18R1	ENST00000677287.1		n.*1574G>C	non_coding_transcript_exon	Exon 11 of 11	ENSP00000503023.1
IL18R1	ENST00000409599.5	TSL:5	c.*404G>C	3_prime_UTR	Exon 12 of 12	ENSP00000387211.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over