2-102332359-C-T

Variant names:

• chr2-102332359-C-T
• rs1420102
• NM_016232.5:c.-149-5757C>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.-149-5757C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,936 control chromosomes in the GnomAD database, including 18,648 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 0.49 (18648 hom., cov: 32)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.-149-5757C>T		intron	N/A	NP_057316.3
	IL1RL1	NM_001282408.2		c.-146-6622C>T		intron	N/A	NP_001269337.1	Q01638-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.-149-5757C>T		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000908526.1		c.-149-5757C>T		intron	N/A	ENSP00000578585.1
	IL18R1	ENST00000410040.5	TSL:2	c.-29+20736C>T		intron	N/A	ENSP00000386663.1	Q13478

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74895 AN: 151816 Hom.: 18626 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.493 AC: 74954 AN: 151936 Hom.: 18648 Cov.: 32 AF XY: 0.490 AC XY: 36377 AN XY: 74240

African (AFR) AF: 0.472 AC: 19562 AN: 41452

American (AMR) AF: 0.406 AC: 6199 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1810 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2755 AN: 5162

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5161 AN: 10522

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35676 AN: 67938

Other (OTH) AF: 0.522 AC: 1100 AN: 2106

Alfa AF: 0.509 Hom.: 6156

Bravo AF: 0.482

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.34
PhyloP100		-1.1
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: rs1420102; hg19: chr2-102948819; COSMIC: COSV52113859; COSMIC: COSV52113859;