rs3771172

Positions:

• chr2-102369352-C-T

Variant summary

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

The NM_003855.5(IL18R1):​c.302+1284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,070 control chromosomes in the GnomAD database, including 4,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.22 (4354 hom., cov: 33)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.54

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 (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18R1	NM_003855.5	c.302+1284C>T		intron_variant		ENST00000233957.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000233957.7	c.302+1284C>T		intron_variant		5	NM_003855.5	P1
IL18R1	ENST00000409599.5	c.302+1284C>T		intron_variant		5		P1
IL18R1	ENST00000410040.5	c.302+1284C>T		intron_variant		2
IL18R1	ENST00000677287.1	c.302+1284C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33179 AN: 151952 Hom.: 4352 Cov.: 33

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.218 AC: 33187 AN: 152070 Hom.: 4354 Cov.: 33 AF XY: 0.218 AC XY: 16210 AN XY: 74320

Gnomad4 AFR AF: 0.0899

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.222

Alfa AF: 0.238 Hom.: 888

Bravo AF: 0.204

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.54

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: rs3771172; hg19: chr2-102985812;