2-102338193-C-T

Position:

• chr2-102338193-C-T

Variant summary

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

The ENST00000233954(IL1RL1):​c.-72C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 976,016 control chromosomes in the GnomAD database, including 11,460 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 0.17 (2645 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8815 hom.)
• Consequence: IL1RL1 ENST00000233954 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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]

IL1RL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.-72C>T		5_prime_UTR_premature_start_codon_gain_variant	2/11	ENST00000233954.6	NP_057316.3
IL1RL1	NM_016232.5	c.-72C>T		5_prime_UTR_variant	2/11	ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954	c.-72C>T		5_prime_UTR_premature_start_codon_gain_variant	2/11	1	NM_016232.5	ENSP00000233954.1
IL1RL1	ENST00000233954	c.-72C>T		5_prime_UTR_variant	2/11	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26514 AN: 151946 Hom.: 2640 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.139 AC: 114189 AN: 823954 Hom.: 8815 Cov.: 11 AF XY: 0.136 AC XY: 59124 AN XY: 433958

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.0868

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.0647

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.175 AC: 26542 AN: 152062 Hom.: 2645 Cov.: 32 AF XY: 0.173 AC XY: 12825 AN XY: 74328

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.170

Alfa AF: 0.144 Hom.: 1158

Bravo AF: 0.174

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
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: rs13431828; hg19: chr2-102954653; COSMIC: COSV52113384;