2-113104596-G-A

Variant names:

• chr2-113104596-G-A
• rs17042888
• ENST00000409052.6:n.-472+5007G>A

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-472+5007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,166 control chromosomes in the GnomAD database, including 1,278 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 (1278 hom., cov: 32)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409052.6	TSL:5	n.-472+5007G>A		intron	N/A	ENSP00000387210.1
	IL1RN	ENST00000463073.6	TSL:5	n.103+5007G>A		intron	N/A
	IL1RN	ENST00000465812.6	TSL:5	n.276-2618G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18070 AN: 152048 Hom.: 1282 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.0887

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

GnomAD4 genome AF: 0.119 AC: 18065 AN: 152166 Hom.: 1278 Cov.: 32 AF XY: 0.122 AC XY: 9104 AN XY: 74424

African (AFR) AF: 0.151 AC: 6271 AN: 41482

American (AMR) AF: 0.143 AC: 2184 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1447 AN: 5174

South Asian (SAS) AF: 0.108 AC: 522 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1574 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0828 AC: 5629 AN: 68012

Other (OTH) AF: 0.0887 AC: 187 AN: 2108

Alfa AF: 0.0919 Hom.: 1879

Bravo AF: 0.120

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.74
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs17042888; hg19: chr2-113862173;