rs13029918

chr2-102340831-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016232.5(IL1RL1):c.610+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,567,136 control chromosomes in the GnomAD database, including 474 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 0.017 (29 hom., cov: 32)
  • Exomes 𝑓: 0.023 (445 hom.)
• Consequence: IL1RL1 NM_016232.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.001017
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.65).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0169 (2580/152280) while in subpopulation NFE AF= 0.0254 (1727/68022). AF 95% confidence interval is 0.0244. There are 29 homozygotes in gnomad4. There are 1210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.610+3A>G		splice_donor_region_variant, intron_variant		ENST00000233954.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.610+3A>G		splice_donor_region_variant, intron_variant		1	NM_016232.5	P1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2580 AN: 152162 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0158 AC: 3228 AN: 204298 Hom.: 38 AF XY: 0.0162 AC XY: 1812 AN XY: 111972

Gnomad AFR exome AF: 0.00398

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.000490

Gnomad SAS exome AF: 0.00400

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0231 AC: 32724 AN: 1414856 Hom.: 445 Cov.: 30 AF XY: 0.0227 AC XY: 15966 AN XY: 703394

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.00405

Gnomad4 FIN exome AF: 0.0104

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0169 AC: 2580 AN: 152280 Hom.: 29 Cov.: 32 AF XY: 0.0162 AC XY: 1210 AN XY: 74462

Gnomad4 AFR AF: 0.00534

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0205 Hom.: 20

Bravo AF: 0.0168

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	7.6
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0010
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13029918; hg19: chr2-102957291;