2-102374909-G-A

Variant names:

• chr2-102374909-G-A
• rs6758936
• NM_003855.5:c.469-998G>A

Variant summary

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

The NM_003855.5(IL18R1):​c.469-998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,086 control chromosomes in the GnomAD database, including 23,585 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: 33)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.469-998G>A		intron_variant	Intron 4 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.469-998G>A		intron_variant	Intron 4 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.469-998G>A		intron_variant	Intron 5 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.469-998G>A		intron_variant	Intron 4 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*12+916G>A		intron_variant	Intron 4 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81227 AN: 151968 Hom.: 23552 Cov.: 33

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.525

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 81313 AN: 152086 Hom.: 23585 Cov.: 33 AF XY: 0.529 AC XY: 39296 AN XY: 74348

African (AFR) AF: 0.731 AC: 30328 AN: 41482

American (AMR) AF: 0.413 AC: 6318 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2130 AN: 3472

East Asian (EAS) AF: 0.151 AC: 781 AN: 5178

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

European-Finnish (FIN) AF: 0.543 AC: 5736 AN: 10556

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

European-Non Finnish (NFE) AF: 0.486 AC: 33051 AN: 67964

Other (OTH) AF: 0.521 AC: 1100 AN: 2112

Alfa AF: 0.495 Hom.: 75181

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.29
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: rs6758936; hg19: chr2-102991369; COSMIC: COSV52123403; COSMIC: COSV52123403;