2-102318777-T-C

Variant names:

• chr2-102318777-T-C
• rs11123918
• NM_016232.5:c.-150+7154T>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.-150+7154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,906 control chromosomes in the GnomAD database, including 17,701 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 0.48 (17701 hom., cov: 31)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.-150+7154T>C		intron	N/A	NP_057316.3
	IL1RL1	NM_001282408.2		c.-147+7154T>C		intron	N/A	NP_001269337.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.-150+7154T>C		intron	N/A	ENSP00000233954.1
	IL18R1	ENST00000410040.5	TSL:2	c.-29+7154T>C		intron	N/A	ENSP00000386663.1
	IL1RL1	ENST00000404917.6	TSL:2	c.-147+7154T>C		intron	N/A	ENSP00000384822.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72674 AN: 151788 Hom.: 17682 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.479 AC: 72725 AN: 151906 Hom.: 17701 Cov.: 31 AF XY: 0.475 AC XY: 35295 AN XY: 74228

African (AFR) AF: 0.421 AC: 17427 AN: 41400

American (AMR) AF: 0.402 AC: 6137 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2740 AN: 5160

South Asian (SAS) AF: 0.440 AC: 2120 AN: 4820

European-Finnish (FIN) AF: 0.489 AC: 5148 AN: 10532

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35671 AN: 67920

Other (OTH) AF: 0.515 AC: 1089 AN: 2114

Alfa AF: 0.461 Hom.: 3746

Bravo AF: 0.466

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.81
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11123918; hg19: chr2-102935237; COSMIC: COSV52113686;