ENST00000259206.9:c.73+3242T>C

Variant names:

• chr2-113123370-T-C
• rs315936
• ENST00000259206.9:c.73+3242T>C

Variant summary

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

The ENST00000259206.9(IL1RN):​c.73+3242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,108 control chromosomes in the GnomAD database, including 43,828 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 0.76 (43828 hom., cov: 31)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259206.9. 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+3242T>C		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.11-4319T>C		intron	N/A	NP_000568.1	P18510-2
	IL1RN	NM_001318914.2		c.-39+1752T>C		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+3242T>C		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.11-4319T>C		intron	N/A	ENSP00000329072.3	P18510-2
	IL1RN	ENST00000361779.7	TSL:1	c.-39+1752T>C		intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115170 AN: 151990 Hom.: 43803 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.758 AC: 115242 AN: 152108 Hom.: 43828 Cov.: 31 AF XY: 0.757 AC XY: 56274 AN XY: 74350

African (AFR) AF: 0.802 AC: 33289 AN: 41492

American (AMR) AF: 0.703 AC: 10726 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2470 AN: 3468

East Asian (EAS) AF: 0.923 AC: 4779 AN: 5180

South Asian (SAS) AF: 0.719 AC: 3468 AN: 4822

European-Finnish (FIN) AF: 0.741 AC: 7839 AN: 10578

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50166 AN: 67994

Other (OTH) AF: 0.740 AC: 1558 AN: 2104

Alfa AF: 0.753 Hom.: 5470

Bravo AF: 0.759

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.39
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs315936;

hg19: chr2-113880947;