rs3732127

Positions:

• chr2-102397290-G-C
• chr2-102397290-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.*404G>C		3_prime_UTR_variant	11/11	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.*404G>C		3_prime_UTR_variant	11/11	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.*404G>C		3_prime_UTR_variant	12/12	5		ENSP00000387211.1
IL18R1	ENST00000677287.1	n.*1574G>C		non_coding_transcript_exon_variant	11/11			ENSP00000503023.1
IL18R1	ENST00000677287.1	n.*1574G>C		3_prime_UTR_variant	11/11			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32908 AN: 152020 Hom.: 4047 Cov.: 32

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.: 0 AF XY: 0.144 AC XY: 755 AN XY: 5236

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.0548

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.217 AC: 32939 AN: 152138 Hom.: 4049 Cov.: 32 AF XY: 0.213 AC XY: 15844 AN XY: 74376

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.212

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
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs3732127; hg19: chr2-103013750; COSMIC: COSV52123612; COSMIC: COSV52123612;