rs1946131

Positions:

• chr2-102345469-C-T

Variant summary

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

The ENST00000311734.6(IL1RL1):​c.*2037C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 985,002 control chromosomes in the GnomAD database, including 5,273 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 0.11 (978 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4295 hom.)
• Consequence: IL1RL1 ENST00000311734.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.970+2054C>T		intron_variant		ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000311734.6	c.*2037C>T		3_prime_UTR_variant	8/8	1		ENSP00000310371
IL1RL1	ENST00000233954.6	c.970+2054C>T		intron_variant		1	NM_016232.5	ENSP00000233954	P1
IL1RL1	ENST00000404917.6	c.*2037C>T		3_prime_UTR_variant	7/7	2		ENSP00000384822
IL18R1	ENST00000410040.5	c.-28-17164C>T		intron_variant		2		ENSP00000386663

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16641 AN: 152046 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.101 AC: 84089 AN: 832840 Hom.: 4295 Cov.: 31 AF XY: 0.101 AC XY: 38960 AN XY: 384590

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.0485

Gnomad4 SAS exome AF: 0.0916

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0999

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.110 AC: 16662 AN: 152162 Hom.: 978 Cov.: 32 AF XY: 0.110 AC XY: 8196 AN XY: 74400

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.136

Alfa AF: 0.104 Hom.: 550

Bravo AF: 0.108

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.60

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: rs1946131; hg19: chr2-102961929;