ENST00000409052.6:n.-273+1360G>A

Variant names:

• chr2-113100447-G-A
• ENST00000409052.6:n.-472+858G>A

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-472+858G>A 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: 32)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 0 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: 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-472+858G>A		intron_variant	Intron 1 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-644+858G>A		intron_variant	Intron 1 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-601+858G>A		intron_variant	Intron 1 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-409+858G>A		intron_variant	Intron 1 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-472+858G>A		intron_variant	Intron 1 of 9	5		ENSP00000387210.1
IL1RN	ENST00000463073.6	n.103+858G>A		intron_variant	Intron 1 of 3	5
IL1RN	ENST00000465812.6	n.275+858G>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.56
PhyloP100		-0.88

Splicing

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

Other links and lift over

hg19: chr2-113858024;