rs2071459

chr2-113129906-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173842.3(IL1RN):c.205+242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 504,864 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3103 hom., cov: 32)
  • Exomes 𝑓: 0.17 (8222 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.604

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-113129906-C-T is Benign according to our data. Variant chr2-113129906-C-T is described in ClinVar as [Benign]. Clinvar id is 537717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.205+242C>T		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.205+242C>T		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27265 AN: 151948 Hom.: 3106 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.174 AC: 61385 AN: 352798 Hom.: 8222 Cov.: 0 AF XY: 0.170 AC XY: 31733 AN XY: 187084

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.179 AC: 27269 AN: 152066 Hom.: 3103 Cov.: 32 AF XY: 0.184 AC XY: 13709 AN XY: 74312

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.166

Alfa AF: 0.158 Hom.: 288

Bravo AF: 0.179

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

This variant is associated with the following publications: (PMID: 23462747, 27884173) -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.4
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071459; hg19: chr2-113887483;