rs12905

Variant names:

• chr2-102343547-G-A
• rs12905
• ENST00000311734.6:c.*115G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102343547-G-A
• chr2-102343547-G-C
• chr2-102343547-G-T

Variant summary

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

The NM_003856.4(IL1RL1):​c.*115G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,564,902 control chromosomes in the GnomAD database, including 59,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4269 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55046 hom.)
• Consequence: IL1RL1 NM_003856.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 27 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=-0.9).
• 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+132G>A		intron	N/A	NP_057316.3
	IL1RL1	NM_003856.4		c.*115G>A		3_prime_UTR	Exon 8 of 8	NP_003847.2
	IL1RL1	NM_001282408.2		c.*115G>A		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.*115G>A		3_prime_UTR	Exon 8 of 8	ENSP00000310371.2	Q01638-2
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.970+132G>A		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000427077.1	TSL:1	n.*492G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000391120.1	Q01638-3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33119 AN: 152028 Hom.: 4268 Cov.: 33

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.275 AC: 388876 AN: 1412756 Hom.: 55046 Cov.: 34 AF XY: 0.276 AC XY: 192699 AN XY: 698234

African (AFR) AF: 0.0870 AC: 2833 AN: 32556

American (AMR) AF: 0.163 AC: 6694 AN: 41086

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3595 AN: 23548

East Asian (EAS) AF: 0.387 AC: 15204 AN: 39258

South Asian (SAS) AF: 0.283 AC: 22557 AN: 79580

European-Finnish (FIN) AF: 0.272 AC: 11623 AN: 42770

Middle Eastern (MID) AF: 0.173 AC: 864 AN: 4988

European-Non Finnish (NFE) AF: 0.285 AC: 310260 AN: 1090362

Other (OTH) AF: 0.260 AC: 15246 AN: 58608

GnomAD4 genome AF: 0.218 AC: 33126 AN: 152146 Hom.: 4269 Cov.: 33 AF XY: 0.218 AC XY: 16183 AN XY: 74378

African (AFR) AF: 0.0969 AC: 4026 AN: 41542

American (AMR) AF: 0.180 AC: 2746 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2031 AN: 5158

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4822

European-Finnish (FIN) AF: 0.264 AC: 2788 AN: 10576

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

European-Non Finnish (NFE) AF: 0.279 AC: 18982 AN: 67976

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.197 Hom.: 1851

Bravo AF: 0.204

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12905; hg19: chr2-102960007; COSMIC: COSV52114889; COSMIC: COSV52114889;