2-102314488-A-G

Variant names:

• chr2-102314488-A-G
• rs12712135
• NM_016232.5:c.-150+2865A>G

Variant summary

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

The NM_016232.5(IL1RL1):​c.-150+2865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,072 control chromosomes in the GnomAD database, including 23,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.55 (23022 hom., cov: 33)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.444
• Publications: 24 publications found

Genes affected

IL1RL1 (HGNC:5998): (interleukin 1 receptor like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.-150+2865A>G		intron_variant	Intron 1 of 10	ENST00000233954.6	NP_057316.3
IL1RL1	NM_001282408.2	c.-147+2865A>G		intron_variant	Intron 1 of 6		NP_001269337.1
IL1RL1	XM_011512151.2	c.-150+2865A>G		intron_variant	Intron 1 of 7		XP_011510453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.-150+2865A>G		intron_variant	Intron 1 of 10	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82800 AN: 151954 Hom.: 22986 Cov.: 33

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.545 AC: 82887 AN: 152072 Hom.: 23022 Cov.: 33 AF XY: 0.540 AC XY: 40151 AN XY: 74330

African (AFR) AF: 0.643 AC: 26667 AN: 41496

American (AMR) AF: 0.424 AC: 6482 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1872 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2922 AN: 5164

South Asian (SAS) AF: 0.444 AC: 2143 AN: 4824

European-Finnish (FIN) AF: 0.489 AC: 5175 AN: 10578

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35855 AN: 67958

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.520 Hom.: 26320

Bravo AF: 0.543

Asia WGS AF: 0.535 AC: 1863 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.9
DANN	Benign	0.54
PhyloP100		0.44
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: rs12712135; hg19: chr2-102930948; COSMIC: COSV52113586;