2-113126106-A-G

Variant names:

• chr2-113126106-A-G
• rs4252001
• ENST00000259206.9:c.74-1583A>G

Variant summary

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

The ENST00000259206.9(IL1RN):​c.74-1583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,132 control chromosomes in the GnomAD database, including 3,203 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 (3203 hom., cov: 32)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.74-1583A>G		intron_variant	Intron 2 of 5		NP_776213.1
IL1RN	NM_000577.5	c.11-1583A>G		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-38-1583A>G		intron_variant	Intron 3 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.74-1583A>G		intron_variant	Intron 2 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.11-1583A>G		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-38-1583A>G		intron_variant	Intron 2 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27736 AN: 152014 Hom.: 3205 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.170

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27743 AN: 152132 Hom.: 3203 Cov.: 32 AF XY: 0.188 AC XY: 13969 AN XY: 74358

African (AFR) AF: 0.235 AC: 9732 AN: 41498

American (AMR) AF: 0.144 AC: 2193 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3468

East Asian (EAS) AF: 0.581 AC: 3005 AN: 5170

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

European-Finnish (FIN) AF: 0.247 AC: 2611 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8691 AN: 68002

Other (OTH) AF: 0.168 AC: 354 AN: 2110

Alfa AF: 0.102 Hom.: 201

Bravo AF: 0.181

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.28
PhyloP100		-1.2
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: rs4252001; hg19: chr2-113883683;