rs17207494

Variant names:

• chr2-113106433-A-C
• rs17207494
• ENST00000409052.6:n.-471-4683A>C

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-471-4683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,146 control chromosomes in the GnomAD database, including 8,356 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 0.32 (8356 hom., cov: 33)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409052.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409052.6	TSL:5	n.-471-4683A>C		intron	N/A	ENSP00000387210.1
	IL1RN	ENST00000463073.6	TSL:5	n.104-4683A>C		intron	N/A
	IL1RN	ENST00000465812.6	TSL:5	n.276-781A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48467 AN: 152028 Hom.: 8350 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.319 AC: 48491 AN: 152146 Hom.: 8356 Cov.: 33 AF XY: 0.314 AC XY: 23310 AN XY: 74354

African (AFR) AF: 0.232 AC: 9629 AN: 41510

American (AMR) AF: 0.321 AC: 4900 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3470

East Asian (EAS) AF: 0.0672 AC: 349 AN: 5192

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4804

European-Finnish (FIN) AF: 0.299 AC: 3163 AN: 10580

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26067 AN: 67990

Other (OTH) AF: 0.355 AC: 747 AN: 2106

Alfa AF: 0.334 Hom.: 1113

Bravo AF: 0.318

Asia WGS AF: 0.257 AC: 892 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.67
PhyloP100		-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17207494; hg19: chr2-113864010;