NM_003855.5:c.*404G>A

Variant names:

• chr2-102397290-G-A
• rs3732127
• NM_003855.5:c.*404G>A

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.*404G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 9,790 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: 0.00010 (0 hom.)
• Consequence: IL18R1 NM_003855.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• 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=-0.86).

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.*404G>A		3_prime_UTR	Exon 11 of 11	NP_003846.1
	IL18R1	NM_001371418.1		c.*404G>A		3_prime_UTR	Exon 11 of 11	NP_001358347.1
	IL18R1	NM_001371421.1		c.*404G>A		3_prime_UTR	Exon 13 of 13	NP_001358350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.*404G>A		3_prime_UTR	Exon 11 of 11	ENSP00000233957.1
	IL18R1	ENST00000677287.1		n.*1574G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000503023.1
	IL18R1	ENST00000409599.5	TSL:5	c.*404G>A		3_prime_UTR	Exon 12 of 12	ENSP00000387211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000102 AC: 1 AN: 9790 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 5248

African (AFR) AF: 0.00 AC: 0 AN: 160

American (AMR) AF: 0.00 AC: 0 AN: 876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 192

East Asian (EAS) AF: 0.00 AC: 0 AN: 420

South Asian (SAS) AF: 0.00 AC: 0 AN: 748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.000152 AC: 1 AN: 6572

Other (OTH) AF: 0.00 AC: 0 AN: 504

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.62
PhyloP100		-0.69

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: rs3732127; hg19: chr2-103013750;