rs17027006

Positions:

• chr2-102348872-G-C
• chr2-102348872-G-T

Variant summary

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

The ENST00000233954.6(IL1RL1):​c.1118-207G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,038 control chromosomes in the GnomAD database, including 4,373 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 0.22 (4373 hom., cov: 32)
• Consequence: IL1RL1 ENST00000233954.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.1118-207G>C		intron_variant		ENST00000233954.6	NP_057316.3
IL1RL1	XM_006712839.4	c.1118-207G>C		intron_variant			XP_006712902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.1118-207G>C		intron_variant		1	NM_016232.5	ENSP00000233954	P1
IL18R1	ENST00000410040.5	c.-28-13761G>C		intron_variant		2		ENSP00000386663

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33517 AN: 151920 Hom.: 4372 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.220 AC: 33523 AN: 152038 Hom.: 4373 Cov.: 32 AF XY: 0.220 AC XY: 16364 AN XY: 74318

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.224

Alfa AF: 0.144 Hom.: 285

Bravo AF: 0.207

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.73

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: rs17027006; hg19: chr2-102965332; COSMIC: COSV52118285; COSMIC: COSV52118285;