rs1794068

Variant names:

• chr2-113128926-G-A
• rs1794068
• NM_173842.3:c.117-650G>A

Variant summary

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

The NM_173842.3(IL1RN):​c.117-650G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,072 control chromosomes in the GnomAD database, including 4,292 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 (4292 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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.117-650G>A		intron	N/A	NP_776214.1
	IL1RN	NM_173841.3		c.126-650G>A		intron	N/A	NP_776213.1
	IL1RN	NM_000577.5		c.63-650G>A		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.117-650G>A		intron	N/A	ENSP00000387173.3
	IL1RN	ENST00000259206.9	TSL:1	c.126-650G>A		intron	N/A	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.63-650G>A		intron	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32820 AN: 151952 Hom.: 4284 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0769

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.216 AC: 32856 AN: 152072 Hom.: 4292 Cov.: 32 AF XY: 0.219 AC XY: 16257 AN XY: 74326

African (AFR) AF: 0.0710 AC: 2946 AN: 41516

American (AMR) AF: 0.283 AC: 4328 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3472

East Asian (EAS) AF: 0.0763 AC: 393 AN: 5150

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4812

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10570

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18770 AN: 67968

Other (OTH) AF: 0.240 AC: 505 AN: 2106

Alfa AF: 0.228 Hom.: 699

Bravo AF: 0.206

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.32
PhyloP100		-0.83
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: rs1794068; hg19: chr2-113886503; COSMIC: COSV52080035;