rs439154

Variant names:

• chr2-113126824-G-A
• rs439154
• ENST00000259206.9:c.74-865G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113126824-G-A
• chr2-113126824-G-C
• chr2-113126824-G-T

Variant summary

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

The ENST00000259206.9(IL1RN):​c.74-865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,974 control chromosomes in the GnomAD database, including 12,887 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 0.40 (12887 hom., cov: 32)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.74-865G>A		intron_variant	Intron 2 of 5		NP_776213.1
IL1RN	NM_000577.5	c.11-865G>A		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-38-865G>A		intron_variant	Intron 3 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.74-865G>A		intron_variant	Intron 2 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.11-865G>A		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-38-865G>A		intron_variant	Intron 2 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61257 AN: 151856 Hom.: 12874 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.403 AC: 61310 AN: 151974 Hom.: 12887 Cov.: 32 AF XY: 0.412 AC XY: 30569 AN XY: 74274

African (AFR) AF: 0.321 AC: 13295 AN: 41426

American (AMR) AF: 0.433 AC: 6613 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1402 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3417 AN: 5158

South Asian (SAS) AF: 0.403 AC: 1943 AN: 4818

European-Finnish (FIN) AF: 0.554 AC: 5842 AN: 10540

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27454 AN: 67972

Other (OTH) AF: 0.412 AC: 867 AN: 2106

Alfa AF: 0.389 Hom.: 1961

Bravo AF: 0.393

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		0.47
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: rs439154; hg19: chr2-113884401; COSMIC: COSV52080009; COSMIC: COSV52080009;