2-218782181-CCATGGCTGCG-C
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000784.4(CYP27A1):c.1_10delATGGCTGCGC(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
CYP27A1
NM_000784.4 frameshift, start_lost
NM_000784.4 frameshift, start_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.08
Genes affected
CYP27A1 (HGNC:2605): (cytochrome P450 family 27 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein oxidizes cholesterol intermediates as part of the bile synthesis pathway. Since the conversion of cholesterol to bile acids is the major route for removing cholesterol from the body, this protein is important for overall cholesterol homeostasis. Mutations in this gene cause cerebrotendinous xanthomatosis, a rare autosomal recessive lipid storage disease. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 35 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-218782181-CCATGGCTGCG-C is Pathogenic according to our data. Variant chr2-218782181-CCATGGCTGCG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3585662.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.1_10delATGGCTGCGC | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 9 | 1 | NM_000784.4 | ENSP00000258415.4 | ||
CYP27A1 | ENST00000445971.1 | n.1_10delATGGCTGCGC | non_coding_transcript_exon_variant | Exon 1 of 5 | 5 | ENSP00000404945.1 | ||||
CYP27A1 | ENST00000466602.1 | n.10_19delATGGCTGCGC | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | |||||
CYP27A1 | ENST00000494263.5 | n.435_444delATGGCTGCGC | non_coding_transcript_exon_variant | Exon 1 of 7 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.23e-7 AC: 1AN: 1383938Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 683018
GnomAD4 exome
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1
AN:
1383938
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AN XY:
683018
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cholestanol storage disease Pathogenic:1
Mar 14, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.