2-102343821-C-G

Variant names:

• chr2-102343821-C-G
• rs3821204
• ENST00000311734.6:c.*389C>G

Variant summary

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

The NM_003856.4(IL1RL1):​c.*389C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,027,474 control chromosomes in the GnomAD database, including 39,601 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 (4269 hom., cov: 32)
  • Exomes 𝑓: 0.28 (35332 hom.)
• Consequence: IL1RL1 NM_003856.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 29 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003856.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.970+406C>G		intron	N/A	NP_057316.3
	IL1RL1	NM_003856.4		c.*389C>G		3_prime_UTR	Exon 8 of 8	NP_003847.2
	IL1RL1	NM_001282408.2		c.*389C>G		3_prime_UTR	Exon 7 of 7	NP_001269337.1	Q01638-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000311734.6	TSL:1	c.*389C>G		3_prime_UTR	Exon 8 of 8	ENSP00000310371.2	Q01638-2
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.970+406C>G		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000409584.5	TSL:5	c.*389C>G		3_prime_UTR	Exon 8 of 8	ENSP00000386618.1	E9PC41

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33056 AN: 151980 Hom.: 4268 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.282 AC: 246640 AN: 875374 Hom.: 35332 Cov.: 28 AF XY: 0.282 AC XY: 114815 AN XY: 406672

African (AFR) AF: 0.0769 AC: 1400 AN: 18210

American (AMR) AF: 0.163 AC: 784 AN: 4820

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 977 AN: 6398

East Asian (EAS) AF: 0.379 AC: 2705 AN: 7142

South Asian (SAS) AF: 0.273 AC: 5406 AN: 19776

European-Finnish (FIN) AF: 0.238 AC: 349 AN: 1468

Middle Eastern (MID) AF: 0.193 AC: 339 AN: 1758

European-Non Finnish (NFE) AF: 0.288 AC: 226794 AN: 786344

Other (OTH) AF: 0.268 AC: 7886 AN: 29458

GnomAD4 genome AF: 0.217 AC: 33062 AN: 152100 Hom.: 4269 Cov.: 32 AF XY: 0.217 AC XY: 16142 AN XY: 74338

African (AFR) AF: 0.0940 AC: 3901 AN: 41488

American (AMR) AF: 0.179 AC: 2740 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1344 AN: 4826

European-Finnish (FIN) AF: 0.263 AC: 2781 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19045 AN: 67986

Other (OTH) AF: 0.218 AC: 460 AN: 2110

Alfa AF: 0.151 Hom.: 323

Bravo AF: 0.204

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.68
PhyloP100		-2.0
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: rs3821204; hg19: chr2-102960281;