rs13029918

Variant names:

• chr2-102340831-A-G
• rs13029918
• NM_016232.5:c.610+3A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016232.5(IL1RL1):​c.610+3A>G variant causes a splice 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. 2/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.001017
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 14 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=-0.65).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

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.610+3A>G		splice_region intron	N/A	NP_057316.3
	IL1RL1	NM_003856.4		c.610+3A>G		splice_region intron	N/A	NP_003847.2
	IL1RL1	NM_001282408.2		c.259+3A>G		splice_region intron	N/A	NP_001269337.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.610+3A>G		splice_region intron	N/A	ENSP00000233954.1
	IL1RL1	ENST00000311734.6	TSL:1	c.610+3A>G		splice_region intron	N/A	ENSP00000310371.2
	IL1RL1	ENST00000427077.1	TSL:1	n.610+3A>G		splice_region intron	N/A	ENSP00000391120.1

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

GnomAD2 exomes AF: 0.0158 AC: 3228 AN: 204298 AF XY: 0.0162

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 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

African (AFR) AF: 0.00357 AC: 107 AN: 29938

American (AMR) AF: 0.0139 AC: 425 AN: 30580

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 333 AN: 24146

East Asian (EAS) AF: 0.000133 AC: 5 AN: 37662

South Asian (SAS) AF: 0.00405 AC: 321 AN: 79170

European-Finnish (FIN) AF: 0.0104 AC: 550 AN: 53034

Middle Eastern (MID) AF: 0.0304 AC: 170 AN: 5590

European-Non Finnish (NFE) AF: 0.0270 AC: 29651 AN: 1096446

Other (OTH) AF: 0.0199 AC: 1162 AN: 58290

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

African (AFR) AF: 0.00534 AC: 222 AN: 41554

American (AMR) AF: 0.0216 AC: 331 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4822

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0254 AC: 1727 AN: 68022

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0217 Hom.: 71

Bravo AF: 0.0168

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.6
DANN	Benign	0.49
PhyloP100		1.6
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13029918; hg19: chr2-102957291;