2-102396928-TG-T

Variant names:

• chr2-102396928-TG-T
• rs11465656
• NM_003855.5:c.*46delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003855.5(IL18R1):​c.*46delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,242,206 control chromosomes in the GnomAD database, including 714 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (49 hom., cov: 32)
  • Exomes 𝑓: 0.031 (665 hom.)
• Consequence: IL18R1 NM_003855.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 2 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0243 (3706/152304) while in subpopulation NFE AF = 0.0373 (2534/68026). AF 95% confidence interval is 0.036. There are 49 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

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.*46delG		3_prime_UTR	Exon 11 of 11	NP_003846.1
	IL18R1	NM_001371418.1		c.*46delG		3_prime_UTR	Exon 11 of 11	NP_001358347.1
	IL18R1	NM_001371421.1		c.*46delG		3_prime_UTR	Exon 13 of 13	NP_001358350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.*46delG		3_prime_UTR	Exon 11 of 11	ENSP00000233957.1
	IL18R1	ENST00000677287.1		n.*1216delG		non_coding_transcript_exon	Exon 11 of 11	ENSP00000503023.1
	IL18R1	ENST00000409599.5	TSL:5	c.*46delG		3_prime_UTR	Exon 12 of 12	ENSP00000387211.1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3708 AN: 152186 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00680

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.0273 AC: 4533 AN: 166066 AF XY: 0.0285

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.000475

Gnomad FIN exome AF: 0.0382

Gnomad NFE exome AF: 0.0348

Gnomad OTH exome AF: 0.0333

GnomAD4 exome AF: 0.0314 AC: 34217 AN: 1089902 Hom.: 665 Cov.: 13 AF XY: 0.0318 AC XY: 17503 AN XY: 549648

African (AFR) AF: 0.00505 AC: 126 AN: 24960

American (AMR) AF: 0.0186 AC: 537 AN: 28922

Ashkenazi Jewish (ASJ) AF: 0.00483 AC: 91 AN: 18850

East Asian (EAS) AF: 0.000899 AC: 34 AN: 37834

South Asian (SAS) AF: 0.0381 AC: 2483 AN: 65170

European-Finnish (FIN) AF: 0.0375 AC: 1868 AN: 49862

Middle Eastern (MID) AF: 0.0193 AC: 93 AN: 4828

European-Non Finnish (NFE) AF: 0.0341 AC: 27715 AN: 812102

Other (OTH) AF: 0.0268 AC: 1270 AN: 47374

GnomAD4 genome AF: 0.0243 AC: 3706 AN: 152304 Hom.: 49 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74466

African (AFR) AF: 0.00678 AC: 282 AN: 41574

American (AMR) AF: 0.0139 AC: 212 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4826

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0373 AC: 2534 AN: 68026

Other (OTH) AF: 0.0213 AC: 45 AN: 2116

Alfa AF: 0.0293 Hom.: 24

Bravo AF: 0.0211

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21
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: rs11465656; hg19: chr2-103013388; COSMIC: COSV52122520; COSMIC: COSV52122520;