2-102314488-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.-150+2865A>G		intron_variant		ENST00000233954.6
IL1RL1	NM_001282408.2	c.-147+2865A>G		intron_variant
IL1RL1	XM_011512151.2	c.-150+2865A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.-150+2865A>G		intron_variant		1	NM_016232.5	P1

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.561

Alfa AF: 0.516 Hom.: 19673

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

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	-0.91
Cadd	Benign	6.9
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: rs12712135; hg19: chr2-102930948; COSMIC: COSV52113586;