2-102355405-G-T

Position:

• chr2-102355405-G-T

Variant summary

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

The ENST00000410040.5(IL18R1):​c.-28-7228G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,142 control chromosomes in the GnomAD database, including 45,767 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 (45767 hom., cov: 33)
• Consequence: IL18R1 ENST00000410040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000410040.5	c.-28-7228G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116777 AN: 152022 Hom.: 45718 Cov.: 33

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.768 AC: 116878 AN: 152142 Hom.: 45767 Cov.: 33 AF XY: 0.762 AC XY: 56661 AN XY: 74374

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.763

Alfa AF: 0.758 Hom.: 90997

Bravo AF: 0.756

Asia WGS AF: 0.591 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13015714; hg19: chr2-102971865; COSMIC: COSV52114133;