rs2241116

Variant names:

• chr2-102386805-C-A
• rs2241116
• NM_003855.5:c.810-56C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102386805-C-A
• chr2-102386805-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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 -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.

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.810-56C>A		intron	N/A	NP_003846.1
	IL18R1	NM_001371418.1		c.810-56C>A		intron	N/A	NP_001358347.1
	IL18R1	NM_001371419.1		c.810-56C>A		intron	N/A	NP_001358348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.810-56C>A		intron	N/A	ENSP00000233957.1
	IL18R1	ENST00000409599.5	TSL:5	c.810-56C>A		intron	N/A	ENSP00000387211.1
	IL18R1	ENST00000410040.5	TSL:2	c.810-56C>A		intron	N/A	ENSP00000386663.1

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

African (AFR) AF: 0.0612 AC: 1956 AN: 31950

American (AMR) AF: 0.137 AC: 5704 AN: 41676

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3233 AN: 25622

East Asian (EAS) AF: 0.201 AC: 7903 AN: 39366

South Asian (SAS) AF: 0.230 AC: 19100 AN: 83060

European-Finnish (FIN) AF: 0.221 AC: 11734 AN: 53214

Middle Eastern (MID) AF: 0.156 AC: 879 AN: 5642

European-Non Finnish (NFE) AF: 0.216 AC: 232086 AN: 1072910

Other (OTH) AF: 0.197 AC: 11534 AN: 58668

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

African (AFR) AF: 0.0684 AC: 2843 AN: 41536

American (AMR) AF: 0.144 AC: 2198 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1187 AN: 5176

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4818

European-Finnish (FIN) AF: 0.207 AC: 2192 AN: 10574

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14651 AN: 67980

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.189 Hom.: 8225

Bravo AF: 0.156

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Ascending aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		-0.27
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: rs2241116; hg19: chr2-103003265; COSMIC: COSV52126384;