rs451578

Variant names:

• chr2-113130980-G-A
• rs451578
• NM_173842.3:c.206-65G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113130980-G-A
• chr2-113130980-G-C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.966
• 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 -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 rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.206-65G>A		intron_variant	Intron 2 of 3	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.206-65G>A		intron_variant	Intron 2 of 3	1	NM_173842.3	ENSP00000387173.3

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

African (AFR) AF: 0.0686 AC: 1516 AN: 22108

American (AMR) AF: 0.325 AC: 14059 AN: 43204

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 6633 AN: 22368

East Asian (EAS) AF: 0.0592 AC: 2192 AN: 37008

South Asian (SAS) AF: 0.286 AC: 21181 AN: 73944

European-Finnish (FIN) AF: 0.311 AC: 16148 AN: 52004

Middle Eastern (MID) AF: 0.219 AC: 970 AN: 4436

European-Non Finnish (NFE) AF: 0.289 AC: 164960 AN: 571048

Other (OTH) AF: 0.263 AC: 10711 AN: 40746

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

African (AFR) AF: 0.0718 AC: 2981 AN: 41508

American (AMR) AF: 0.289 AC: 4414 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3470

East Asian (EAS) AF: 0.0772 AC: 400 AN: 5178

South Asian (SAS) AF: 0.293 AC: 1414 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3293 AN: 10532

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19716 AN: 67914

Other (OTH) AF: 0.247 AC: 521 AN: 2112

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.56
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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