ENST00000259206.9:c.11-148G>C

Variant names:

• chr2-113119918-G-C
• rs928940
• ENST00000259206.9:c.11-148G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000259206.9(IL1RN):​c.11-148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 19 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.11-148G>C		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.10+1890G>C		intron	N/A	NP_000568.1	P18510-2
	IL1RN	NM_001318914.2		c.-272-148G>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.11-148G>C		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.10+1890G>C		intron	N/A	ENSP00000329072.3	P18510-2
	IL1RN	ENST00000361779.7	TSL:1	c.-209-1530G>C		intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 561730 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 298068

African (AFR) AF: 0.00 AC: 0 AN: 15300

American (AMR) AF: 0.00 AC: 0 AN: 31492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18306

East Asian (EAS) AF: 0.00 AC: 0 AN: 31458

South Asian (SAS) AF: 0.00 AC: 0 AN: 58778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3348

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 325572

Other (OTH) AF: 0.00 AC: 0 AN: 29992

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 6154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.064
PhyloP100		-0.088

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: rs928940;

hg19: chr2-113877495;