2-102393077-C-T

Position:

• chr2-102393077-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.1112-1392C>T 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 151,964 control chromosomes in the GnomAD database, including 23,576 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 (23576 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.1112-1392C>T		intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.1112-1392C>T		intron_variant		5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.1112-1392C>T		intron_variant		5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.1112-1392C>T		intron_variant		2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*656-1392C>T		intron_variant				ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81188 AN: 151846 Hom.: 23545 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.542

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: 81272 AN: 151964 Hom.: 23576 Cov.: 32 AF XY: 0.529 AC XY: 39257 AN XY: 74272

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.520

Alfa AF: 0.446 Hom.: 8214

Bravo AF: 0.536

Asia WGS AF: 0.230 AC: 800 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4851004; hg19: chr2-103009537; COSMIC: COSV52123588;