2-102338193-C-T

Variant names:

• chr2-102338193-C-T
• rs13431828
• NM_016232.5:c.-72C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016232.5(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 NM_016232.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• Publications: 60 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=-0.84).
• 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 rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.-72C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	ENST00000233954.6	NP_057316.3
IL1RL1	NM_016232.5	c.-72C>T		5_prime_UTR_variant	Exon 2 of 11	ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.-72C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	1	NM_016232.5	ENSP00000233954.1
IL1RL1	ENST00000233954.6	c.-72C>T		5_prime_UTR_variant	Exon 2 of 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

African (AFR) AF: 0.269 AC: 5559 AN: 20664

American (AMR) AF: 0.0868 AC: 3472 AN: 39982

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 4670 AN: 21192

East Asian (EAS) AF: 0.126 AC: 4479 AN: 35500

South Asian (SAS) AF: 0.0647 AC: 4315 AN: 66736

European-Finnish (FIN) AF: 0.166 AC: 8535 AN: 51464

Middle Eastern (MID) AF: 0.131 AC: 582 AN: 4442

European-Non Finnish (NFE) AF: 0.141 AC: 77066 AN: 545212

Other (OTH) AF: 0.142 AC: 5511 AN: 38762

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

African (AFR) AF: 0.263 AC: 10913 AN: 41450

American (AMR) AF: 0.126 AC: 1920 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 741 AN: 3472

East Asian (EAS) AF: 0.0953 AC: 494 AN: 5182

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1796 AN: 10566

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9785 AN: 67972

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.147 Hom.: 1467

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
PhyloP100		0.53
Mutation Taster		=300/0	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: rs13431828; hg19: chr2-102954653; COSMIC: COSV52113384;