rs447713

Variant names:

• chr2-113130095-A-G
• rs447713
• NM_173842.3:c.205+431A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-113130095-A-G
• chr2-113130095-A-T

Variant summary

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

The NM_173842.3(IL1RN):​c.205+431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 193,634 control chromosomes in the GnomAD database, including 5,222 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 0.22 (4290 hom., cov: 32)
  • Exomes 𝑓: 0.20 (932 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.277 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173842.3	MANE Select	c.205+431A>G		intron	N/A	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.214+431A>G		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.151+431A>G		intron	N/A	NP_000568.1	P18510-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.205+431A>G		intron	N/A	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.214+431A>G		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.151+431A>G		intron	N/A	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32850 AN: 152028 Hom.: 4282 Cov.: 32

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.196 AC: 8150 AN: 41488 Hom.: 932 Cov.: 0 AF XY: 0.197 AC XY: 4255 AN XY: 21560

African (AFR) AF: 0.0434 AC: 105 AN: 2422

American (AMR) AF: 0.293 AC: 1063 AN: 3624

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 184 AN: 900

East Asian (EAS) AF: 0.0520 AC: 179 AN: 3444

South Asian (SAS) AF: 0.213 AC: 1036 AN: 4858

European-Finnish (FIN) AF: 0.219 AC: 219 AN: 1002

Middle Eastern (MID) AF: 0.179 AC: 29 AN: 162

European-Non Finnish (NFE) AF: 0.215 AC: 4964 AN: 23120

Other (OTH) AF: 0.190 AC: 371 AN: 1956

GnomAD4 genome AF: 0.216 AC: 32888 AN: 152146 Hom.: 4290 Cov.: 32 AF XY: 0.219 AC XY: 16279 AN XY: 74372

African (AFR) AF: 0.0709 AC: 2944 AN: 41532

American (AMR) AF: 0.284 AC: 4339 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.0772 AC: 400 AN: 5184

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3224 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18788 AN: 67976

Other (OTH) AF: 0.238 AC: 502 AN: 2108

Alfa AF: 0.180 Hom.: 613

Bravo AF: 0.206

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.46
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs447713; hg19: chr2-113887672; COSMIC: COSV52080116; COSMIC: COSV52080116;