rs3755278

Variant names:

• chr2-102335757-T-C
• rs3755278
• NM_016232.5:c.-149-2359T>C

Variant summary

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

The NM_016232.5(IL1RL1):​c.-149-2359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 152,210 control chromosomes in the GnomAD database, including 585 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 0.083 (585 hom., cov: 32)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.-149-2359T>C		intron_variant	Intron 1 of 10	ENST00000233954.6	NP_057316.3
IL1RL1	NM_001282408.2	c.-146-3224T>C		intron_variant	Intron 1 of 6		NP_001269337.1
IL1RL1	XM_011512151.2	c.-149-2359T>C		intron_variant	Intron 1 of 7		XP_011510453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.-149-2359T>C		intron_variant	Intron 1 of 10	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12620 AN: 152092 Hom.: 586 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.0830 AC: 12635 AN: 152210 Hom.: 585 Cov.: 32 AF XY: 0.0818 AC XY: 6085 AN XY: 74426

African (AFR) AF: 0.0709 AC: 2946 AN: 41534

American (AMR) AF: 0.0931 AC: 1423 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5176

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4826

European-Finnish (FIN) AF: 0.0431 AC: 457 AN: 10606

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.0921 AC: 6265 AN: 68008

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.0851 Hom.: 149

Bravo AF: 0.0860

Asia WGS AF: 0.0700 AC: 242 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.41
PhyloP100		0.11
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: rs3755278; hg19: chr2-102952217;