rs1420103

Positions:

• chr2-102332172-A-C
• chr2-102332172-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016232.5(IL1RL1):​c.-149-5944A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,138 control chromosomes in the GnomAD database, including 47,164 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 0.78 (47164 hom., cov: 32)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.-149-5944A>C		intron_variant		ENST00000233954.6
IL1RL1	NM_001282408.2	c.-146-6809A>C		intron_variant
IL1RL1	XM_011512151.2	c.-149-5944A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.-149-5944A>C		intron_variant		1	NM_016232.5	P1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118122 AN: 152018 Hom.: 47108 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.777 AC: 118231 AN: 152138 Hom.: 47164 Cov.: 32 AF XY: 0.769 AC XY: 57151 AN XY: 74364

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.772

Alfa AF: 0.778 Hom.: 11325

Bravo AF: 0.774

Asia WGS AF: 0.597 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.88
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs1420103; hg19: chr2-102948632;