rs2287033

Variant names:

• chr2-102394777-T-C
• rs2287033
• NM_003855.5:c.1270+150T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.1270+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 498,388 control chromosomes in the GnomAD database, including 61,193 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 (23585 hom., cov: 32)
  • Exomes 𝑓: 0.44 (37608 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• 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=-0.87).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	NM_003855.5	MANE Select	c.1270+150T>C		intron	N/A	NP_003846.1
	IL18R1	NM_001371418.1		c.1267+150T>C		intron	N/A	NP_001358347.1
	IL18R1	NM_001371421.1		c.805+150T>C		intron	N/A	NP_001358350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.1270+150T>C		intron	N/A	ENSP00000233957.1
	IL18R1	ENST00000409599.5	TSL:5	c.1270+150T>C		intron	N/A	ENSP00000387211.1
	IL18R1	ENST00000410040.5	TSL:2	c.1270+150T>C		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81196 AN: 151908 Hom.: 23553 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.440 AC: 152386 AN: 346360 Hom.: 37608 AF XY: 0.430 AC XY: 77338 AN XY: 179748

African (AFR) AF: 0.738 AC: 7383 AN: 10002

American (AMR) AF: 0.334 AC: 4460 AN: 13334

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 5287 AN: 8834

East Asian (EAS) AF: 0.161 AC: 3801 AN: 23660

South Asian (SAS) AF: 0.241 AC: 6204 AN: 25776

European-Finnish (FIN) AF: 0.529 AC: 15586 AN: 29466

Middle Eastern (MID) AF: 0.546 AC: 695 AN: 1274

European-Non Finnish (NFE) AF: 0.466 AC: 100546 AN: 215864

Other (OTH) AF: 0.464 AC: 8424 AN: 18150

GnomAD4 genome AF: 0.535 AC: 81282 AN: 152028 Hom.: 23585 Cov.: 32 AF XY: 0.529 AC XY: 39290 AN XY: 74332

African (AFR) AF: 0.732 AC: 30329 AN: 41444

American (AMR) AF: 0.413 AC: 6311 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.149 AC: 774 AN: 5182

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4824

European-Finnish (FIN) AF: 0.543 AC: 5741 AN: 10564

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

European-Non Finnish (NFE) AF: 0.486 AC: 33026 AN: 67948

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.481 Hom.: 12063

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		0.031
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: rs2287033; hg19: chr2-103011237;