rs3771172

Variant names:

• chr2-102369352-C-T
• rs3771172
• NM_003855.5:c.302+1284C>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.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
• Publications: 13 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=-0.89).
• 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 rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.302+1284C>T		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.302+1284C>T		intron_variant	Intron 3 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.302+1284C>T		intron_variant	Intron 4 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.302+1284C>T		intron_variant	Intron 3 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.302+1284C>T		intron_variant	Intron 2 of 10			ENSP00000503023.1

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

African (AFR) AF: 0.0899 AC: 3731 AN: 41490

American (AMR) AF: 0.181 AC: 2763 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2003 AN: 5166

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4818

European-Finnish (FIN) AF: 0.270 AC: 2852 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19311 AN: 67966

Other (OTH) AF: 0.222 AC: 469 AN: 2112

Alfa AF: 0.258 Hom.: 7611

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

Feb 01, 2021

Beijing Anzhen Hospital, Capital Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.54
PhyloP100		-1.5
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: rs3771172; hg19: chr2-102985812;