chr2-102368164-C-G

Variant names:

• chr2-102368164-C-G
• rs1362348
• NM_003855.5:c.302+96C>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.302+96C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,340,974 control chromosomes in the GnomAD database, including 101,414 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 0.44 (16460 hom., cov: 33)
  • Exomes 𝑓: 0.37 (84954 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 21 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	NM_003855.5	MANE Select	c.302+96C>G		intron	N/A	NP_003846.1	Q13478
	IL18R1	NM_001371418.1		c.302+96C>G		intron	N/A	NP_001358347.1	B7ZKV7
	IL18R1	NM_001371419.1		c.302+96C>G		intron	N/A	NP_001358348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.302+96C>G		intron	N/A	ENSP00000233957.1	Q13478
	IL18R1	ENST00000409599.5	TSL:5	c.302+96C>G		intron	N/A	ENSP00000387211.1	Q13478
	IL18R1	ENST00000410040.5	TSL:2	c.302+96C>G		intron	N/A	ENSP00000386663.1	Q13478

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66732 AN: 152032 Hom.: 16435 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.366 AC: 435685 AN: 1188824 Hom.: 84954 AF XY: 0.360 AC XY: 214585 AN XY: 596248

African (AFR) AF: 0.667 AC: 18372 AN: 27524

American (AMR) AF: 0.226 AC: 8669 AN: 38352

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 10000 AN: 21270

East Asian (EAS) AF: 0.152 AC: 5787 AN: 38058

South Asian (SAS) AF: 0.184 AC: 13231 AN: 72098

European-Finnish (FIN) AF: 0.414 AC: 20973 AN: 50610

Middle Eastern (MID) AF: 0.280 AC: 1408 AN: 5028

European-Non Finnish (NFE) AF: 0.383 AC: 338586 AN: 885168

Other (OTH) AF: 0.368 AC: 18659 AN: 50716

GnomAD4 genome AF: 0.439 AC: 66806 AN: 152150 Hom.: 16460 Cov.: 33 AF XY: 0.432 AC XY: 32170 AN XY: 74382

African (AFR) AF: 0.658 AC: 27313 AN: 41498

American (AMR) AF: 0.313 AC: 4786 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3472

East Asian (EAS) AF: 0.129 AC: 668 AN: 5188

South Asian (SAS) AF: 0.199 AC: 961 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4472 AN: 10594

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25665 AN: 67980

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.409 Hom.: 1708

Bravo AF: 0.443

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.32
PhyloP100		-0.37
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: rs1362348; hg19: chr2-102984624; COSMIC: COSV52123329;