2-102378560-G-A

Variant names:

• chr2-102378560-G-A
• rs2080289
• NM_003855.5:c.625+2497G>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.625+2497G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,094 control chromosomes in the GnomAD database, including 4,763 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 0.24 (4763 hom., cov: 33)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	NM_003855.5	MANE Select	c.625+2497G>A		intron	N/A	NP_003846.1
	IL18R1	NM_001371418.1		c.625+2497G>A		intron	N/A	NP_001358347.1
	IL18R1	NM_001371419.1		c.625+2497G>A		intron	N/A	NP_001358348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.625+2497G>A		intron	N/A	ENSP00000233957.1
	IL18R1	ENST00000409599.5	TSL:5	c.625+2497G>A		intron	N/A	ENSP00000387211.1
	IL18R1	ENST00000410040.5	TSL:2	c.625+2497G>A		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36167 AN: 151974 Hom.: 4765 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.238 AC: 36176 AN: 152094 Hom.: 4763 Cov.: 33 AF XY: 0.238 AC XY: 17670 AN XY: 74350

African (AFR) AF: 0.157 AC: 6522 AN: 41482

American (AMR) AF: 0.189 AC: 2897 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2094 AN: 5168

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4828

European-Finnish (FIN) AF: 0.270 AC: 2852 AN: 10564

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19182 AN: 67976

Other (OTH) AF: 0.236 AC: 497 AN: 2110

Alfa AF: 0.173 Hom.: 587

Bravo AF: 0.227

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.76
PhyloP100		-1.4
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: rs2080289; hg19: chr2-102995020;