chr2-113131068-G-T
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_173842.3(IL1RN):c.229G>T(p.Glu77*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_173842.3 stop_gained
Scores
Clinical Significance
Conservation
Publications
- sterile multifocal osteomyelitis with periostitis and pustulosisInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000318 AC: 8AN: 251474 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460318Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726582 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74362 show subpopulations
ClinVar
Submissions by phenotype
not provided Pathogenic:3Other:1
- -
- -
- -
- -
Sterile multifocal osteomyelitis with periostitis and pustulosis Pathogenic:2
This sequence change creates a premature translational stop signal (p.Glu80*) in the IL1RN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL1RN are known to be pathogenic (PMID: 19494218, 21792839, 22940634, 26100510). This variant is present in population databases (rs121913161, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with interleukin 1 receptor antagonist deficiency (PMID: 19494218). This variant is also known as c.229G>T (E77X). ClinVar contains an entry for this variant (Variation ID: 14675). For these reasons, this variant has been classified as Pathogenic. -
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at