rs12905

Positions:

• chr2-102343547-G-A
• chr2-102343547-G-C
• chr2-102343547-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000311734.6(IL1RL1):​c.*115G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,564,902 control chromosomes in the GnomAD database, including 59,315 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 0.22 (4269 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55046 hom.)
• Consequence: IL1RL1 ENST00000311734.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.970+132G>A		intron_variant		ENST00000233954.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.970+132G>A		intron_variant		1	NM_016232.5	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33119 AN: 152028 Hom.: 4268 Cov.: 33

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.275 AC: 388876 AN: 1412756 Hom.: 55046 Cov.: 34 AF XY: 0.276 AC XY: 192699 AN XY: 698234

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.387

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.218 AC: 33126 AN: 152146 Hom.: 4269 Cov.: 33 AF XY: 0.218 AC XY: 16183 AN XY: 74378

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.218

Alfa AF: 0.218 Hom.: 1452

Bravo AF: 0.204

Asia WGS AF: 0.339 AC: 1181 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	0.10
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs12905; hg19: chr2-102960007; COSMIC: COSV52114889; COSMIC: COSV52114889;