rs9807989

Positions:

• chr2-102354740-T-C
• chr2-102354740-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000410040.5(IL18R1):​c.-28-7893T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,952 control chromosomes in the GnomAD database, including 17,707 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 0.45 (17707 hom., cov: 32)
• Consequence: IL18R1 ENST00000410040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000410040.5	c.-28-7893T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68536 AN: 151834 Hom.: 17678 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.452 AC: 68615 AN: 151952 Hom.: 17707 Cov.: 32 AF XY: 0.444 AC XY: 33008 AN XY: 74270

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.409

Alfa AF: 0.416 Hom.: 1810

Bravo AF: 0.458

Asia WGS AF: 0.181 AC: 630 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9807989; hg19: chr2-102971200; COSMIC: COSV52114115;