rs72551323
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000784.4(CYP27A1):c.1471G>A(p.Ala491Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,614,064 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A491S) has been classified as Likely benign.
Frequency
Consequence
NM_000784.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP27A1 | NM_000784.4 | c.1471G>A | p.Ala491Thr | missense_variant | 8/9 | ENST00000258415.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.1471G>A | p.Ala491Thr | missense_variant | 8/9 | 1 | NM_000784.4 | P1 | |
CYP27A1 | ENST00000494263.5 | n.2183G>A | non_coding_transcript_exon_variant | 6/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000227 AC: 57AN: 250604Hom.: 0 AF XY: 0.000317 AC XY: 43AN XY: 135496
GnomAD4 exome AF: 0.000140 AC: 205AN: 1461758Hom.: 2 Cov.: 32 AF XY: 0.000184 AC XY: 134AN XY: 727172
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 27, 2023 | BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 26, 2018 | - - |
Cholestanol storage disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at