rs315921

Variant names:

• chr2-113114474-G-A
• rs315921
• ENST00000409052.6:n.-273+1360G>A

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-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 ENST00000409052.6 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: 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-273+1360G>A		intron_variant	Intron 3 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-273+1360G>A		intron_variant	Intron 4 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-402+1360G>A		intron_variant	Intron 3 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-210+1360G>A		intron_variant	Intron 3 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-273+1360G>A		intron_variant	Intron 3 of 9	5		ENSP00000387210.1
IL1RN	ENST00000463073.6	n.303-1031G>A		intron_variant	Intron 3 of 3	5
IL1RN	ENST00000465812.6	n.646+1360G>A		intron_variant	Intron 4 of 5	5

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 v4.3

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;