rs1794066

Variant names:

• chr2-113128773-A-G
• rs1794066
• NM_173842.3:c.117-803A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-113128773-A-G
• chr2-113128773-A-T

Variant summary

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

The NM_173842.3(IL1RN):​c.117-803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,098 control chromosomes in the GnomAD database, including 14,439 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 0.43 (14439 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 9 publications found

Genes affected

IL1RN (HGNC:6000): (interleukin 1 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173842.3. 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
	IL1RN	NM_173842.3	MANE Select	c.117-803A>G		intron	N/A	NP_776214.1
	IL1RN	NM_173841.3		c.126-803A>G		intron	N/A	NP_776213.1
	IL1RN	NM_000577.5		c.63-803A>G		intron	N/A	NP_000568.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.117-803A>G		intron	N/A	ENSP00000387173.3
	IL1RN	ENST00000259206.9	TSL:1	c.126-803A>G		intron	N/A	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.63-803A>G		intron	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65456 AN: 151980 Hom.: 14427 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.431 AC: 65507 AN: 152098 Hom.: 14439 Cov.: 32 AF XY: 0.438 AC XY: 32547 AN XY: 74378

African (AFR) AF: 0.415 AC: 17232 AN: 41490

American (AMR) AF: 0.442 AC: 6760 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3403 AN: 5166

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4820

European-Finnish (FIN) AF: 0.553 AC: 5855 AN: 10584

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27502 AN: 67966

Other (OTH) AF: 0.428 AC: 903 AN: 2112

Alfa AF: 0.415 Hom.: 2026

Bravo AF: 0.425

Asia WGS AF: 0.523 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.44
PhyloP100		0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1794066; hg19: chr2-113886350; COSMIC: COSV52080023;