chr2-102394452-C-T

Variant names:

• chr2-102394452-C-T
• rs1420096
• NM_003855.5:c.1112-17C>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.1112-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,570,424 control chromosomes in the GnomAD database, including 185,344 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 0.53 (23574 hom., cov: 31)
  • Exomes 𝑓: 0.47 (161770 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 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.1112-17C>T		intron	N/A	NP_003846.1
	IL18R1	NM_001371418.1		c.1109-17C>T		intron	N/A	NP_001358347.1
	IL18R1	NM_001371421.1		c.647-17C>T		intron	N/A	NP_001358350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.1112-17C>T		intron	N/A	ENSP00000233957.1
	IL18R1	ENST00000409599.5	TSL:5	c.1112-17C>T		intron	N/A	ENSP00000387211.1
	IL18R1	ENST00000410040.5	TSL:2	c.1112-17C>T		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81178 AN: 151832 Hom.: 23543 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

GnomAD2 exomes AF: 0.434 AC: 102512 AN: 236108 AF XY: 0.428

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.466 AC: 661291 AN: 1418474 Hom.: 161770 Cov.: 25 AF XY: 0.460 AC XY: 324579 AN XY: 705122

African (AFR) AF: 0.746 AC: 23740 AN: 31812

American (AMR) AF: 0.292 AC: 11670 AN: 39904

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15016 AN: 24562

East Asian (EAS) AF: 0.166 AC: 6515 AN: 39236

South Asian (SAS) AF: 0.260 AC: 21364 AN: 82292

European-Finnish (FIN) AF: 0.535 AC: 28170 AN: 52630

Middle Eastern (MID) AF: 0.587 AC: 3279 AN: 5590

European-Non Finnish (NFE) AF: 0.483 AC: 523565 AN: 1083892

Other (OTH) AF: 0.478 AC: 27972 AN: 58556

GnomAD4 genome AF: 0.535 AC: 81262 AN: 151950 Hom.: 23574 Cov.: 31 AF XY: 0.529 AC XY: 39240 AN XY: 74232

African (AFR) AF: 0.732 AC: 30345 AN: 41450

American (AMR) AF: 0.413 AC: 6305 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2133 AN: 3472

East Asian (EAS) AF: 0.151 AC: 779 AN: 5174

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5715 AN: 10542

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33014 AN: 67922

Other (OTH) AF: 0.522 AC: 1102 AN: 2112

Alfa AF: 0.524 Hom.: 4174

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.60
PhyloP100		-1.4
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: rs1420096; hg19: chr2-103010912; COSMIC: COSV52123223;