rs315921

Variant names:

• chr2-113114474-G-A
• rs315921
• XM_011511121.2:c.-273+1360G>A

Variant summary

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

The XM_011511121.2(IL1RN):​c.-273+1360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,180 control chromosomes in the GnomAD database, including 1,463 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 0.12 (1463 hom., cov: 32)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409052.6	TSL:5	n.-273+1360G>A		intron	N/A	ENSP00000387210.1	P18510-4
	IL1RN	ENST00000463073.6	TSL:5	n.303-1031G>A		intron	N/A
	IL1RN	ENST00000465812.6	TSL:5	n.646+1360G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18023 AN: 152062 Hom.: 1464 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.118 AC: 18015 AN: 152180 Hom.: 1463 Cov.: 32 AF XY: 0.116 AC XY: 8593 AN XY: 74386

African (AFR) AF: 0.0315 AC: 1308 AN: 41546

American (AMR) AF: 0.0966 AC: 1477 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5178

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4818

European-Finnish (FIN) AF: 0.139 AC: 1469 AN: 10564

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12461 AN: 68000

Other (OTH) AF: 0.116 AC: 246 AN: 2112

Alfa AF: 0.153 Hom.: 503

Bravo AF: 0.112

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.77
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs315921; hg19: chr2-113872051;