chr2-102349850-G-A

Variant names:

• chr2-102349850-G-A
• rs10208293
• NM_016232.5:c.1285+604G>A

Variant summary

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

The NM_016232.5(IL1RL1):​c.1285+604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,028 control chromosomes in the GnomAD database, including 9,053 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 0.33 (9053 hom., cov: 32)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.1285+604G>A		intron	N/A	NP_057316.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1285+604G>A		intron	N/A	ENSP00000233954.1
	IL18R1	ENST00000410040.5	TSL:2	c.-28-12783G>A		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49468 AN: 151910 Hom.: 9043 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.326 AC: 49514 AN: 152028 Hom.: 9053 Cov.: 32 AF XY: 0.319 AC XY: 23729 AN XY: 74328

African (AFR) AF: 0.492 AC: 20374 AN: 41426

American (AMR) AF: 0.240 AC: 3671 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3472

East Asian (EAS) AF: 0.128 AC: 661 AN: 5182

South Asian (SAS) AF: 0.169 AC: 814 AN: 4826

European-Finnish (FIN) AF: 0.259 AC: 2730 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18956 AN: 67974

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.299 Hom.: 3461

Bravo AF: 0.332

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.21
PhyloP100		-0.17
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: rs10208293; hg19: chr2-102966310;