2-113121720-G-A

Variant names:

• chr2-113121720-G-A
• rs3213448
• ENST00000259206.9:c.73+1592G>A

Variant summary

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

The NM_173841.3(IL1RN):​c.73+1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 605,236 control chromosomes in the GnomAD database, including 7,040 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 0.18 (3184 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3856 hom.)
• Consequence: IL1RN NM_173841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 26 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173841.3. 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_173841.3		c.73+1592G>A		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.10+3692G>A		intron	N/A	NP_000568.1	P18510-2
	IL1RN	NM_001318914.2		c.-39+102G>A		intron	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000259206.9	TSL:1	c.73+1592G>A		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.10+3692G>A		intron	N/A	ENSP00000329072.3	P18510-2
	IL1RN	ENST00000361779.7	TSL:1	c.-39+102G>A		intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27677 AN: 151990 Hom.: 3185 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.123 AC: 55617 AN: 453126 Hom.: 3856 AF XY: 0.122 AC XY: 25956 AN XY: 213494

African (AFR) AF: 0.241 AC: 1963 AN: 8162

American (AMR) AF: 0.112 AC: 61 AN: 546

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 290 AN: 2804

East Asian (EAS) AF: 0.574 AC: 1057 AN: 1840

South Asian (SAS) AF: 0.0957 AC: 859 AN: 8980

European-Finnish (FIN) AF: 0.270 AC: 53 AN: 196

Middle Eastern (MID) AF: 0.129 AC: 118 AN: 916

European-Non Finnish (NFE) AF: 0.119 AC: 49186 AN: 415020

Other (OTH) AF: 0.138 AC: 2030 AN: 14662

GnomAD4 genome AF: 0.182 AC: 27687 AN: 152110 Hom.: 3184 Cov.: 32 AF XY: 0.187 AC XY: 13935 AN XY: 74344

African (AFR) AF: 0.234 AC: 9708 AN: 41494

American (AMR) AF: 0.143 AC: 2193 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2989 AN: 5156

South Asian (SAS) AF: 0.119 AC: 576 AN: 4830

European-Finnish (FIN) AF: 0.247 AC: 2606 AN: 10562

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8684 AN: 67994

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.144 Hom.: 7985

Bravo AF: 0.181

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.25
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3213448; hg19: chr2-113879297;