2-102370753-A-G

Variant names:

• chr2-102370753-A-G
• rs11465597
• NM_003855.5:c.303-1200A>G

Variant summary

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

The NM_003855.5(IL18R1):​c.303-1200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 152,236 control chromosomes in the GnomAD database, including 812 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 0.097 (812 hom., cov: 33)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.303-1200A>G		intron_variant	Intron 3 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.303-1200A>G		intron_variant	Intron 3 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.303-1200A>G		intron_variant	Intron 4 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.303-1200A>G		intron_variant	Intron 3 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.303-1200A>G		intron_variant	Intron 2 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14740 AN: 152118 Hom.: 811 Cov.: 33

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.0969 AC: 14750 AN: 152236 Hom.: 812 Cov.: 33 AF XY: 0.0978 AC XY: 7281 AN XY: 74428

African (AFR) AF: 0.0698 AC: 2901 AN: 41542

American (AMR) AF: 0.100 AC: 1532 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5186

South Asian (SAS) AF: 0.0879 AC: 424 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1274 AN: 10594

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7372 AN: 68000

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.102 Hom.: 581

Bravo AF: 0.0929

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		0.20
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: rs11465597; hg19: chr2-102987213;