rs3771170

Variant names:

• chr2-102369520-T-A
• rs3771170
• NM_003855.5:c.302+1452T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.302+1452T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,162 control chromosomes in the GnomAD database, including 46,656 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 (46656 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.302+1452T>A		intron_variant	Intron 3 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.302+1452T>A		intron_variant	Intron 3 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.302+1452T>A		intron_variant	Intron 4 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.302+1452T>A		intron_variant	Intron 3 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.302+1452T>A		intron_variant	Intron 2 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117790 AN: 152044 Hom.: 46607 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.775 AC: 117892 AN: 152162 Hom.: 46656 Cov.: 32 AF XY: 0.769 AC XY: 57192 AN XY: 74394

African (AFR) AF: 0.892 AC: 37060 AN: 41532

American (AMR) AF: 0.604 AC: 9230 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.559 AC: 2889 AN: 5168

South Asian (SAS) AF: 0.557 AC: 2686 AN: 4820

European-Finnish (FIN) AF: 0.812 AC: 8604 AN: 10594

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52249 AN: 67976

Other (OTH) AF: 0.767 AC: 1614 AN: 2104

Alfa AF: 0.772 Hom.: 5688

Bravo AF: 0.764

Asia WGS AF: 0.589 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.50
PhyloP100		-0.015
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

Other links and lift over

dbSNP: rs3771170; hg19: chr2-102985980; COSMIC: COSV52123348;