rs11677397

Variant names:

• chr2-113117504-C-A
• rs11677397
• ENST00000409052.6:n.-272-2562C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113117504-C-A
• chr2-113117504-C-T

Variant summary

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

The ENST00000409052.6(IL1RN):​n.-272-2562C>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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-272-2562C>A		intron_variant	Intron 3 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-272-2562C>A		intron_variant	Intron 4 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-401-33C>A		intron_variant	Intron 3 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-209-3944C>A		intron_variant	Intron 3 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-272-2562C>A		intron_variant	Intron 3 of 9	5		ENSP00000387210.1
IL1RN	ENST00000465812.6	n.647-33C>A		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12438 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6480

African (AFR) AF: 0.00 AC: 0 AN: 310

American (AMR) AF: 0.00 AC: 0 AN: 2184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 196

East Asian (EAS) AF: 0.00 AC: 0 AN: 746

South Asian (SAS) AF: 0.00 AC: 0 AN: 1406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 32

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6830

Other (OTH) AF: 0.00 AC: 0 AN: 550

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1582

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.41
PhyloP100		-1.4
PromoterAI		-0.063	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11677397; hg19: chr2-113875081;