rs315931

Variant names:

• chr2-113112266-C-A
• rs315931
• ENST00000409052.6:n.-387-734C>A

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-387-734C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,100 control chromosomes in the GnomAD database, including 28,492 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 0.60 (28492 hom., cov: 33)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-387-734C>A		intron_variant	Intron 2 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-387-734C>A		intron_variant	Intron 3 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-516-734C>A		intron_variant	Intron 2 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-324-734C>A		intron_variant	Intron 2 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-387-734C>A		intron_variant	Intron 2 of 9	5		ENSP00000387210.1
IL1RN	ENST00000463073.6	n.188-734C>A		intron_variant	Intron 2 of 3	5
IL1RN	ENST00000465812.6	n.532-734C>A		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91790 AN: 151982 Hom.: 28500 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.604 AC: 91810 AN: 152100 Hom.: 28492 Cov.: 33 AF XY: 0.598 AC XY: 44444 AN XY: 74376

African (AFR) AF: 0.486 AC: 20169 AN: 41462

American (AMR) AF: 0.585 AC: 8947 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1929 AN: 5176

South Asian (SAS) AF: 0.545 AC: 2625 AN: 4816

European-Finnish (FIN) AF: 0.611 AC: 6459 AN: 10566

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47239 AN: 68010

Other (OTH) AF: 0.605 AC: 1278 AN: 2112

Alfa AF: 0.663 Hom.: 130335

Bravo AF: 0.596

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.78
PhyloP100		-0.43
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: rs315931; hg19: chr2-113869843;