rs759724947
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173841.3(IL1RN):c.10+4A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000756 in 1,455,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_173841.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL1RN | NM_173841.3 | c.10+4A>G | splice_region_variant, intron_variant | Intron 1 of 5 | NP_776213.1 | |||
IL1RN | NM_000577.5 | c.10+4A>G | splice_region_variant, intron_variant | Intron 1 of 4 | NP_000568.1 | |||
IL1RN | NM_001318914.2 | c.-273+4A>G | splice_region_variant, intron_variant | Intron 1 of 6 | NP_001305843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL1RN | ENST00000259206.9 | c.10+4A>G | splice_region_variant, intron_variant | Intron 1 of 5 | 1 | ENSP00000259206.5 | ||||
IL1RN | ENST00000354115.6 | c.10+4A>G | splice_region_variant, intron_variant | Intron 1 of 4 | 1 | ENSP00000329072.3 | ||||
IL1RN | ENST00000361779.7 | c.-210+4A>G | splice_region_variant, intron_variant | Intron 1 of 5 | 1 | ENSP00000354816.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251482Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
GnomAD4 exome AF: 0.00000756 AC: 11AN: 1455912Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 724646
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Sterile multifocal osteomyelitis with periostitis and pustulosis Uncertain:1
This variant has not been reported in the literature in individuals affected with IL1RN-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant is present in population databases (rs759724947, gnomAD 0.006%). This sequence change falls in intron 1 of the IL1RN gene. It does not directly change the encoded amino acid sequence of the IL1RN protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at