rs149101812
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000784.4(CYP27A1):c.148G>A(p.Val50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V50V) has been classified as Likely benign.
Frequency
Consequence
NM_000784.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP27A1 | NM_000784.4 | c.148G>A | p.Val50Ile | missense_variant | 1/9 | ENST00000258415.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.148G>A | p.Val50Ile | missense_variant | 1/9 | 1 | NM_000784.4 | P1 | |
CYP27A1 | ENST00000466602.1 | n.157G>A | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
CYP27A1 | ENST00000494263.5 | n.582G>A | non_coding_transcript_exon_variant | 1/7 | 2 | ||||
CYP27A1 | ENST00000445971.1 | c.148G>A | p.Val50Ile | missense_variant, NMD_transcript_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152258Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000890 AC: 22AN: 247262Hom.: 0 AF XY: 0.0000969 AC XY: 13AN XY: 134118
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461026Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 726788
GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 11, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 11, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 28, 2018 | - - |
Cholestanol storage disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at