2-102350323-T-C

Variant names:

• chr2-102350323-T-C
• rs1861246
• NM_016232.5:c.1285+1077T>C

Variant summary

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

The NM_016232.5(IL1RL1):​c.1285+1077T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,224 control chromosomes in the GnomAD database, including 46,016 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 0.77 (46016 hom., cov: 40)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016232.5. 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
	IL1RL1	NM_016232.5	MANE Select	c.1285+1077T>C		intron	N/A	NP_057316.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1285+1077T>C		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000908526.1		c.1285+1077T>C		intron	N/A	ENSP00000578585.1
	IL1RL1	ENST00000908527.1		c.1285+1077T>C		intron	N/A	ENSP00000578586.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117085 AN: 152108 Hom.: 45965 Cov.: 40

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.770 AC: 117188 AN: 152224 Hom.: 46016 Cov.: 40 AF XY: 0.763 AC XY: 56815 AN XY: 74414

African (AFR) AF: 0.875 AC: 36389 AN: 41580

American (AMR) AF: 0.597 AC: 9125 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2895 AN: 5146

South Asian (SAS) AF: 0.558 AC: 2689 AN: 4818

European-Finnish (FIN) AF: 0.812 AC: 8615 AN: 10608

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52299 AN: 67998

Other (OTH) AF: 0.763 AC: 1614 AN: 2114

Alfa AF: 0.661 Hom.: 4350

Bravo AF: 0.758

Asia WGS AF: 0.593 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.54
PhyloP100		-0.19
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: rs1861246; hg19: chr2-102966783;