ClinVar Genomic variation as it relates to human health
NM_000784.4(CYP27A1):c.1151C>T (p.Pro384Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(1); Benign(7); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000784.4(CYP27A1):c.1151C>T (p.Pro384Leu)
Variation ID: 65831 Accession: VCV000065831.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 218814154 (GRCh38) [ NCBI UCSC ] 2: 219678877 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 1, 2013 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000784.4:c.1151C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000775.1:p.Pro384Leu missense NC_000002.12:g.218814154C>T NC_000002.11:g.219678877C>T NG_007959.1:g.37406C>T - Protein change
- P384L
- Other names
- c.1151C>T
- Canonical SPDI
- NC_000002.12:218814153:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00859 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01853
Exome Aggregation Consortium (ExAC) 0.01878
The Genome Aggregation Database (gnomAD), exomes 0.01898
1000 Genomes Project 0.00859
1000 Genomes Project 30x 0.00874
The Genome Aggregation Database (gnomAD) 0.01478
Trans-Omics for Precision Medicine (TOPMed) 0.01512
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CYP27A1 | - | - |
GRCh38 GRCh37 |
1068 | 1097 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
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Feb 1, 2024 | RCV000056071.21 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2021 | RCV000179342.16 | |
Likely benign (4) |
no assertion criteria provided
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- | RCV001698579.5 | |
Benign (1) |
criteria provided, single submitter
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Oct 5, 2020 | RCV002345362.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538767.1
First in ClinVar: Apr 08, 2017 Last updated: Apr 08, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP(all): 241/13006=1.8% (less)
Method: Genome/Exome Filtration
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Benign
(Jul 03, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics Inc
Accession: SCV000613049.1
First in ClinVar: Apr 08, 2017 Last updated: Apr 08, 2017 |
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Benign
(Oct 27, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000518722.4
First in ClinVar: Mar 08, 2017 Last updated: Apr 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Dec 12, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000231576.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cholestanol storage disease
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001298202.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Dec 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002050910.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000305516.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cholestanol storage disease
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136217.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(-)
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criteria provided, single submitter
Method: research
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Cholestanol storage disease
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435237.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The heterozygous p.Pro384Leu variant in CYP27A1 has been identified in 4 individuals with cerebrotendinous xanthomatosis in cis with a frameshift mutation upstream of the variant … (more)
The heterozygous p.Pro384Leu variant in CYP27A1 has been identified in 4 individuals with cerebrotendinous xanthomatosis in cis with a frameshift mutation upstream of the variant (PMID: 10775536), and has also been identified in >3% of South Asian chromosomes and 37 total homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for cerebrotendinous xanthomatosis. (less)
Ethnicity/Population group: Caucasian;Macedonian
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Benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cholestanol storage disease
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001736819.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: mixed
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Benign
(Oct 05, 2020)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002620500.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: 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. (less)
Number of individuals with the variant: 1
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cholestanol storage disease
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001732808.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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pathologic
(Aug 01, 2013)
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no assertion criteria provided
Method: curation
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Cerebrotendinous Xanthomatosis
Affected status: not provided
Allele origin:
not provided
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GeneReviews
Accession: SCV000087134.1
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2013 |
Comment:
Converted during submission to Pathogenic.
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917014.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963340.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978193.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037002.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Benign
(Nov 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Cerebrotendinous xanthomatosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002078799.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Cholestanol storage disease
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV001338877.1
First in ClinVar: Jun 19, 2020 Last updated: Jun 19, 2020 |
Comment:
Variant interpretted as Pathogenic and reported on 05-03-2012 by Lab or GTR ID 504843. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpretted as Pathogenic and reported on 05-03-2012 by Lab or GTR ID 504843. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Obesity (present) , Abnormal facial shape (present) , Myopia (disease) (present) , Hip dysplasia (present)
Indication for testing: Not Provided
Age: 30-39 years
Sex: female
Testing laboratory: Pathway Genomics
Date variant was reported to submitter: 2012-05-03
Testing laboratory interpretation: Pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Cerebrotendinous Xanthomatosis. | Adam MP | - | 2022 | PMID: 20301583 |
Revisiting the morbid genome of Mendelian disorders. | Abouelhoda M | Genome biology | 2016 | PMID: 27884173 |
Analysis of protein-coding genetic variation in 60,706 humans. | Lek M | Nature | 2016 | PMID: 27535533 |
Apparent underdiagnosis of Cerebrotendinous Xanthomatosis revealed by analysis of ~60,000 human exomes. | Appadurai V | Molecular genetics and metabolism | 2015 | PMID: 26643207 |
Cerebrotendinous Xanthomatosis: Report of two cases and a novel genetic mutation in an Indian patient. | Bajaj BK | Journal of neurosciences in rural practice | 2013 | PMID: 24174808 |
Mutation in CYP27A1 identified in family with coronary artery disease. | Inanloorahatloo K | European journal of medical genetics | 2013 | PMID: 24080357 |
Carrier testing for severe childhood recessive diseases by next-generation sequencing. | Bell CJ | Science translational medicine | 2011 | PMID: 21228398 |
A map of human genome variation from population-scale sequencing. | 1000 Genomes Project Consortium | Nature | 2010 | PMID: 20981092 |
A bioinformatics approach for the phenotype prediction of nonsynonymous single nucleotide polymorphisms in human cytochromes P450. | Wang LL | Drug metabolism and disposition: the biological fate of chemicals | 2009 | PMID: 19204079 |
Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis. | Verrips A | Brain : a journal of neurology | 2000 | PMID: 10775536 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP27A1 | - | - | - | - |
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Text-mined citations for rs41272687 ...
HelpRecord last updated Mar 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.