rs2287037

Variant names:

• chr2-102362568-C-A
• rs2287037
• NM_003855.5:c.-28-65C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102362568-C-A
• chr2-102362568-C-G
• chr2-102362568-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003855.5(IL18R1):​c.-28-65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000108 in 922,936 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.-28-65C>A		intron_variant	Intron 1 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.-28-65C>A		intron_variant	Intron 1 of 10	5	NM_003855.5	ENSP00000233957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000108 AC: 1 AN: 922936 Hom.: 0 AF XY: 0.00000214 AC XY: 1 AN XY: 468270

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20100

American (AMR) AF: 0.00 AC: 0 AN: 22906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17308

East Asian (EAS) AF: 0.00 AC: 0 AN: 33498

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 50056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 687324

Other (OTH) AF: 0.00 AC: 0 AN: 40280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.54
PhyloP100		-0.96

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: rs2287037; hg19: chr2-102979028;