11-117986540-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001558.4(IL10RA):c.67+6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,552,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001558.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL10RA | NM_001558.4 | c.67+6G>T | splice_region_variant, intron_variant | Intron 1 of 6 | ENST00000227752.8 | NP_001549.2 | ||
IL10RA | XM_047426882.1 | c.-267G>T | 5_prime_UTR_variant | Exon 1 of 7 | XP_047282838.1 | |||
IL10RA | NR_026691.2 | n.141+6G>T | splice_region_variant, intron_variant | Intron 1 of 7 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000196 AC: 3AN: 152928Hom.: 0 AF XY: 0.0000247 AC XY: 2AN XY: 81100
GnomAD4 exome AF: 0.0000536 AC: 75AN: 1400320Hom.: 0 Cov.: 31 AF XY: 0.0000666 AC XY: 46AN XY: 690904
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74364
ClinVar
Submissions by phenotype
Inflammatory bowel disease 28 Uncertain:1
This sequence change falls in intron 1 of the IL10RA gene. It does not directly change the encoded amino acid sequence of the IL10RA protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with IL10RA-related conditions. 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. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at