2-113132584-G-A

Variant names:

• chr2-113132584-G-A
• rs4252022
• NM_173842.3:c.319-72G>A

Variant summary

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

The NM_173842.3(IL1RN):​c.319-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,377,664 control chromosomes in the GnomAD database, including 145 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 0.019 (84 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (61 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173842.3. 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
	IL1RN	NM_173842.3	MANE Select	c.319-72G>A		intron	N/A	NP_776214.1
	IL1RN	NM_173841.3		c.328-72G>A		intron	N/A	NP_776213.1
	IL1RN	NM_000577.5		c.265-72G>A		intron	N/A	NP_000568.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.319-72G>A		intron	N/A	ENSP00000387173.3
	IL1RN	ENST00000259206.9	TSL:1	c.328-72G>A		intron	N/A	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.265-72G>A		intron	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2936 AN: 152230 Hom.: 84 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00307

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00464 AC: 5688 AN: 1225316 Hom.: 61 AF XY: 0.00434 AC XY: 2697 AN XY: 620946

African (AFR) AF: 0.0579 AC: 1664 AN: 28734

American (AMR) AF: 0.00398 AC: 175 AN: 43922

Ashkenazi Jewish (ASJ) AF: 0.00683 AC: 168 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 38392

South Asian (SAS) AF: 0.00239 AC: 194 AN: 81086

European-Finnish (FIN) AF: 0.00255 AC: 132 AN: 51700

Middle Eastern (MID) AF: 0.00132 AC: 7 AN: 5316

European-Non Finnish (NFE) AF: 0.00336 AC: 3020 AN: 898840

Other (OTH) AF: 0.00622 AC: 328 AN: 52730

GnomAD4 genome AF: 0.0193 AC: 2939 AN: 152348 Hom.: 84 Cov.: 33 AF XY: 0.0184 AC XY: 1368 AN XY: 74502

African (AFR) AF: 0.0607 AC: 2523 AN: 41572

American (AMR) AF: 0.00673 AC: 103 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4830

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00307 AC: 209 AN: 68038

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.0151 Hom.: 9

Bravo AF: 0.0217

Asia WGS AF: 0.00202 AC: 7 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	0.99
DANN	Benign	0.32
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism

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: rs4252022; hg19: chr2-113890161;