rs11465656

chr2-102396928-TG-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003855.5(IL18R1):c.*46del 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

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 -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18R1	NM_003855.5	c.*46del		3_prime_UTR_variant	11/11	ENST00000233957.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000233957.7	c.*46del		3_prime_UTR_variant	11/11	5	NM_003855.5	P1
IL18R1	ENST00000409599.5	c.*46del		3_prime_UTR_variant	12/12	5		P1
IL18R1	ENST00000677287.1	c.*1216del		3_prime_UTR_variant, NMD_transcript_variant	11/11
IL18R1	ENST00000410040.5			downstream_gene_variant		2

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

GnomAD3 exomes AF: 0.0273 AC: 4533 AN: 166066 Hom.: 88 AF XY: 0.0285 AC XY: 2514 AN XY: 88196

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 SAS exome AF: 0.0343

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

Gnomad4 AFR exome AF: 0.00505

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.00483

Gnomad4 EAS exome AF: 0.000899

Gnomad4 SAS exome AF: 0.0381

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0341

Gnomad4 OTH exome AF: 0.0268

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

Gnomad4 AFR AF: 0.00678

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0213

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 v4.3

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: rs11465656; hg19: chr2-103013388;