rs12999542

Variant names:

• chr2-102348932-A-C
• rs12999542
• NM_016232.5:c.1118-147A>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.1118-147A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 610,028 control chromosomes in the GnomAD database, including 4,769 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 0.14 (1668 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3101 hom.)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.1118-147A>C		intron_variant	Intron 9 of 10	ENST00000233954.6	NP_057316.3
IL1RL1	XM_006712839.4	c.1118-147A>C		intron_variant	Intron 9 of 10		XP_006712902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.1118-147A>C		intron_variant	Intron 9 of 10	1	NM_016232.5	ENSP00000233954.1
IL18R1	ENST00000410040.5	c.-28-13701A>C		intron_variant	Intron 1 of 10	2		ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20884 AN: 152092 Hom.: 1667 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.106 AC: 48529 AN: 457818 Hom.: 3101 AF XY: 0.104 AC XY: 25198 AN XY: 241142

African (AFR) AF: 0.217 AC: 2783 AN: 12834

American (AMR) AF: 0.0938 AC: 1905 AN: 20302

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 2089 AN: 13644

East Asian (EAS) AF: 0.0323 AC: 1021 AN: 31602

South Asian (SAS) AF: 0.0869 AC: 3769 AN: 43386

European-Finnish (FIN) AF: 0.119 AC: 3750 AN: 31642

Middle Eastern (MID) AF: 0.306 AC: 753 AN: 2462

European-Non Finnish (NFE) AF: 0.105 AC: 29045 AN: 275738

Other (OTH) AF: 0.130 AC: 3414 AN: 26208

GnomAD4 genome AF: 0.137 AC: 20913 AN: 152210 Hom.: 1668 Cov.: 32 AF XY: 0.137 AC XY: 10226 AN XY: 74418

African (AFR) AF: 0.218 AC: 9032 AN: 41500

American (AMR) AF: 0.110 AC: 1683 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3468

East Asian (EAS) AF: 0.0411 AC: 213 AN: 5182

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10612

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7286 AN: 68024

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.118 Hom.: 2084

Bravo AF: 0.140

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.38
PhyloP100		0.35
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: rs12999542; hg19: chr2-102965392;