2-102386583-T-C

Position:

• chr2-102386583-T-C

Variant summary

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

The NM_003855.5(IL18R1):​c.810-278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,170 control chromosomes in the GnomAD database, including 46,411 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 0.77 (46411 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.810-278T>C		intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.810-278T>C		intron_variant		5	NM_003855.5	ENSP00000233957	P1
IL18R1	ENST00000409599.5	c.810-278T>C		intron_variant		5		ENSP00000387211	P1
IL18R1	ENST00000410040.5	c.810-278T>C		intron_variant		2		ENSP00000386663
IL18R1	ENST00000677287.1	c.*354-278T>C		intron_variant, NMD_transcript_variant				ENSP00000503023

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117479 AN: 152050 Hom.: 46367 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.773 AC: 117574 AN: 152170 Hom.: 46411 Cov.: 32 AF XY: 0.766 AC XY: 57008 AN XY: 74386

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.758

Alfa AF: 0.720 Hom.: 7055

Bravo AF: 0.762

Asia WGS AF: 0.582 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.46

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: rs2241117; hg19: chr2-103003043; COSMIC: COSV52123517;