2-102344124-C-A

Variant names:

• chr2-102344124-C-A
• rs12712142
• ENST00000311734.6:c.*692C>A

Variant summary

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

The ENST00000311734.6(IL1RL1):​c.*692C>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 0.364 in 165,024 control chromosomes in the GnomAD database, including 11,223 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 0.36 (10206 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1017 hom.)
• Consequence: IL1RL1 ENST00000311734.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 31 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.970+709C>A		intron_variant	Intron 8 of 10	ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.970+709C>A		intron_variant	Intron 8 of 10	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55150 AN: 151842 Hom.: 10200 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.375 AC: 4901 AN: 13064 Hom.: 1017 Cov.: 3 AF XY: 0.373 AC XY: 2404 AN XY: 6452

African (AFR) AF: 0.269 AC: 63 AN: 234

American (AMR) AF: 0.210 AC: 37 AN: 176

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 17 AN: 62

East Asian (EAS) AF: 0.431 AC: 25 AN: 58

South Asian (SAS) AF: 0.397 AC: 89 AN: 224

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 17 AN: 34

European-Non Finnish (NFE) AF: 0.380 AC: 4488 AN: 11824

Other (OTH) AF: 0.364 AC: 163 AN: 448

GnomAD4 genome AF: 0.363 AC: 55193 AN: 151960 Hom.: 10206 Cov.: 32 AF XY: 0.362 AC XY: 26920 AN XY: 74276

African (AFR) AF: 0.335 AC: 13876 AN: 41438

American (AMR) AF: 0.293 AC: 4477 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2237 AN: 5164

South Asian (SAS) AF: 0.362 AC: 1738 AN: 4806

European-Finnish (FIN) AF: 0.384 AC: 4053 AN: 10556

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26533 AN: 67932

Other (OTH) AF: 0.381 AC: 803 AN: 2110

Alfa AF: 0.371 Hom.: 9963

Bravo AF: 0.353

Asia WGS AF: 0.423 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.66
PhyloP100		-1.8
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: rs12712142; hg19: chr2-102960584; COSMIC: COSV107236791; COSMIC: COSV107236791;