2-102363164-G-A

Variant names:

• chr2-102363164-G-A
• rs9308857
• NM_003855.5:c.58+446G>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.58+446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,648 control chromosomes in the GnomAD database, including 16,400 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 0.44 (16400 hom., cov: 31)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.58+446G>A		intron_variant	Intron 2 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.58+446G>A		intron_variant	Intron 2 of 10	5	NM_003855.5	ENSP00000233957.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66549 AN: 151534 Hom.: 16375 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.439 AC: 66623 AN: 151648 Hom.: 16400 Cov.: 31 AF XY: 0.433 AC XY: 32080 AN XY: 74104

African (AFR) AF: 0.658 AC: 27225 AN: 41370

American (AMR) AF: 0.314 AC: 4783 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3472

East Asian (EAS) AF: 0.129 AC: 667 AN: 5164

South Asian (SAS) AF: 0.200 AC: 962 AN: 4814

European-Finnish (FIN) AF: 0.424 AC: 4407 AN: 10392

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25642 AN: 67892

Other (OTH) AF: 0.402 AC: 846 AN: 2104

Alfa AF: 0.388 Hom.: 2666

Bravo AF: 0.443

Asia WGS AF: 0.178 AC: 619 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.19
PhyloP100		-0.15
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: rs9308857; hg19: chr2-102979624; COSMIC: COSV52123300; COSMIC: COSV52123300;