rs4851570

Positions:

• chr2-102389927-A-G

Variant summary

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

The NM_003855.5(IL18R1):​c.950-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 699,800 control chromosomes in the GnomAD database, including 25,975 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 (4757 hom., cov: 33)
  • Exomes 𝑓: 0.27 (21218 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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]

IL18R1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.950-129A>G		intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.950-129A>G		intron_variant		5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.950-129A>G		intron_variant		5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.950-129A>G		intron_variant		2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*494-129A>G		intron_variant				ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36117 AN: 152066 Hom.: 4759 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.273 AC: 149427 AN: 547614 Hom.: 21218 AF XY: 0.274 AC XY: 78565 AN XY: 286532

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.237 AC: 36126 AN: 152186 Hom.: 4757 Cov.: 33 AF XY: 0.237 AC XY: 17643 AN XY: 74392

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.237

Alfa AF: 0.258 Hom.: 686

Bravo AF: 0.227

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.29

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: rs4851570; hg19: chr2-103006387; COSMIC: COSV52124250;