2-102363763-G-T

Variant names:

• chr2-102363763-G-T
• rs11465572
• NM_003855.5:c.58+1045G>T

Variant summary

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

The NM_003855.5(IL18R1):​c.58+1045G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 152,220 control chromosomes in the GnomAD database, including 769 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 0.096 (769 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.58+1045G>T		intron_variant	Intron 2 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.58+1045G>T		intron_variant	Intron 2 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.58+1045G>T		intron_variant	Intron 3 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.58+1045G>T		intron_variant	Intron 2 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.58+1045G>T		intron_variant	Intron 1 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 14603 AN: 152102 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.0865

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.0960 AC: 14616 AN: 152220 Hom.: 769 Cov.: 32 AF XY: 0.0968 AC XY: 7207 AN XY: 74420

African (AFR) AF: 0.0729 AC: 3026 AN: 41520

American (AMR) AF: 0.0966 AC: 1477 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3472

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5182

South Asian (SAS) AF: 0.0877 AC: 423 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10600

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7234 AN: 68006

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.0569 Hom.: 98

Bravo AF: 0.0928

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		0.047
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: rs11465572; hg19: chr2-102980223;