rs2029582

Variant names:

• chr2-113106194-T-C
• rs2029582
• ENST00000409052.6:n.-471-4922T>C

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-471-4922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,040 control chromosomes in the GnomAD database, including 24,599 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 0.55 (24599 hom., cov: 33)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-471-4922T>C		intron_variant	Intron 1 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-643-1020T>C		intron_variant	Intron 1 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-600-4922T>C		intron_variant	Intron 1 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-408-4922T>C		intron_variant	Intron 1 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-471-4922T>C		intron_variant	Intron 1 of 9	5		ENSP00000387210.1
IL1RN	ENST00000463073.6	n.104-4922T>C		intron_variant	Intron 1 of 3	5
IL1RN	ENST00000465812.6	n.276-1020T>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84042 AN: 151922 Hom.: 24582 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.553 AC: 84114 AN: 152040 Hom.: 24599 Cov.: 33 AF XY: 0.547 AC XY: 40626 AN XY: 74306

African (AFR) AF: 0.757 AC: 31384 AN: 41466

American (AMR) AF: 0.511 AC: 7810 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1801 AN: 5174

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4814

European-Finnish (FIN) AF: 0.453 AC: 4785 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32664 AN: 67976

Other (OTH) AF: 0.532 AC: 1121 AN: 2108

Alfa AF: 0.510 Hom.: 12849

Bravo AF: 0.568

Asia WGS AF: 0.456 AC: 1582 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		0.096

Splicing

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

Other links and lift over

dbSNP: rs2029582; hg19: chr2-113863771;