chr2-113113086-G-A

Variant names:

• chr2-113113086-G-A
• rs17042917
• XM_011511121.2:c.-301G>A

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-301G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,146 control chromosomes in the GnomAD database, including 1,626 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 0.14 (1626 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL1RN ENST00000409052.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 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.-301G>A		non_coding_transcript_exon	Exon 3 of 10	ENSP00000387210.1	P18510-4
	IL1RN	ENST00000463073.6	TSL:5	n.274G>A		non_coding_transcript_exon	Exon 3 of 4
	IL1RN	ENST00000465812.6	TSL:5	n.618G>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21151 AN: 152028 Hom.: 1632 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.139 AC: 21157 AN: 152146 Hom.: 1626 Cov.: 32 AF XY: 0.142 AC XY: 10567 AN XY: 74382

African (AFR) AF: 0.170 AC: 7055 AN: 41500

American (AMR) AF: 0.164 AC: 2503 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5164

South Asian (SAS) AF: 0.120 AC: 578 AN: 4826

European-Finnish (FIN) AF: 0.168 AC: 1774 AN: 10558

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7233 AN: 68012

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.105 Hom.: 1154

Bravo AF: 0.140

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.22
Mutation Taster		=296/4	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17042917; hg19: chr2-113870663;