rs451578

chr2-113130980-G-A

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.206-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,018,874 control chromosomes in the GnomAD database, including 39,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4576 hom., cov: 30)
  • Exomes 𝑓: 0.27 (35005 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.966

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=-0.95).
• BP6: Variant 2-113130980-G-A is Benign according to our data. Variant chr2-113130980-G-A is described in ClinVar as [Benign]. Clinvar id is 1178461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.206-65G>A		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.206-65G>A		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34013 AN: 151886 Hom.: 4566 Cov.: 30

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.275 AC: 238370 AN: 866866 Hom.: 35005 AF XY: 0.275 AC XY: 125267 AN XY: 455304

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.0592

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.224 AC: 34053 AN: 152008 Hom.: 4576 Cov.: 30 AF XY: 0.226 AC XY: 16818 AN XY: 74292

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.247

Alfa AF: 0.246 Hom.: 982

Bravo AF: 0.214

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	6.3
Dann	Benign	0.56

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: rs451578; hg19: chr2-113888557; COSMIC: COSV52080145; COSMIC: COSV52080145;