rs2241116

chr2-102386805-C-Achr2-102386805-C-T

Variant summary

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

The NM_003855.5(IL18R1):c.810-56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,564,272 control chromosomes in the GnomAD database, including 33,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2482 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31410 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.272

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18R1	NM_003855.5	c.810-56C>A		intron_variant		ENST00000233957.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000233957.7	c.810-56C>A		intron_variant		5	NM_003855.5	P1
IL18R1	ENST00000409599.5	c.810-56C>A		intron_variant		5		P1
IL18R1	ENST00000410040.5	c.810-56C>A		intron_variant		2
IL18R1	ENST00000677287.1	c.*354-56C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25186 AN: 152044 Hom.: 2481 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.208 AC: 294129 AN: 1412108 Hom.: 31410 AF XY: 0.210 AC XY: 147845 AN XY: 704844

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.166 AC: 25191 AN: 152164 Hom.: 2482 Cov.: 32 AF XY: 0.166 AC XY: 12349 AN XY: 74380

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.179

Alfa AF: 0.196 Hom.: 5150

Bravo AF: 0.156

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.3
Dann	Benign	0.40

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: rs2241116; hg19: chr2-103003265; COSMIC: COSV52126384;