rs771819245
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000784.4(CYP27A1):c.1381C>T(p.Gln461Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 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_000784.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP27A1 | NM_000784.4 | c.1381C>T | p.Gln461Ter | stop_gained | 8/9 | ENST00000258415.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.1381C>T | p.Gln461Ter | stop_gained | 8/9 | 1 | NM_000784.4 | P1 | |
CYP27A1 | ENST00000494263.5 | n.2093C>T | non_coding_transcript_exon_variant | 6/7 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250384Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135792
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cholestanol storage disease Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Nov 22, 2022 | _x000D_This variant was identified as compound heterozygous with NM_000784.4:c.1297dup Criteria applied: PVS1, PM3_STR, PM2_SUP - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 597631). This variant is also known as p.Gln428*. This premature translational stop signal has been observed in individuals with Cerebrotendinous xanthomatosis (PMID: 11181744, 20925952). This variant is present in population databases (rs771819245, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln461*) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 20, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at