ClinVar Genomic variation as it relates to human health
NM_000784.4(CYP27A1):c.944_948del (p.Leu315fs)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000784.4(CYP27A1):c.944_948del (p.Leu315fs)
Variation ID: 4265 Accession: VCV000004265.15
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 2q35 2: 218813022-218813026 (GRCh38) [ NCBI UCSC ] 2: 219677745-219677749 (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 Apr 4, 2013 May 1, 2024 Dec 9, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000784.4:c.944_948del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000775.1:p.Leu315fs frameshift NM_000784.3:c.944_948delTGGCC NC_000002.12:g.218813023_218813027del NC_000002.11:g.219677746_219677750del NG_007959.1:g.36275_36279del - Protein change
- L315fs
- Other names
- c.944_948delTGGCC
- Canonical SPDI
- NC_000002.12:218813021:CTGGCC:C
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 |
1081 | 1111 |
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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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Dec 9, 2023 | RCV000004486.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 5, 2018 | RCV000733619.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 16, 2021 | RCV004018554.1 |
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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Pathogenic
(Jun 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000861707.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Apr 03, 2020)
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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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Revvity Omics, Revvity
Accession: SCV002018123.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Mar 22, 2017)
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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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Counsyl
Accession: SCV000789995.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(Aug 08, 2023)
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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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Baylor Genetics
Accession: SCV004192680.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 09, 2023)
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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: SCV001579756.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu315Glnfs*15) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu315Glnfs*15) 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). This variant is present in population databases (rs770589184, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of cerebrotendinous xanthomatosis (PMID: 12000359). This variant is also known as a five nucleotide deletion (TGGCC; nucleotides 965–969 of the cDNA). ClinVar contains an entry for this variant (Variation ID: 4265). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 16, 2021)
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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: SCV003590060.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.944_948delTGGCC (p.L315Qfs*15) alteration, located in exon 5 (coding exon 5) of the CYP27A1 gene, consists of a deletion of 5 nucleotides from position 944 … (more)
The c.944_948delTGGCC (p.L315Qfs*15) alteration, located in exon 5 (coding exon 5) of the CYP27A1 gene, consists of a deletion of 5 nucleotides from position 944 to 948, causing a translational frameshift with a predicted alternate stop codon after 15 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant (referred to as a five nucleotide deletion of TGGCC) co-occurred with a second variant in CYP27A1 gene in an individual reported to have cerebrotendinous xanthomatosis (Lamon-Fava, 2002) Based on the available evidence, this alteration is classified as pathogenic. (less)
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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: SCV000087245.1
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2013 |
Comment:
Converted during submission to Pathogenic.
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Pathogenic
(Mar 01, 2002)
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no assertion criteria provided
Method: literature only
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CEREBROTENDINOUS XANTHOMATOSIS
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024660.2
First in ClinVar: Apr 04, 2013 Last updated: Jan 06, 2024 |
Comment on evidence:
For discussion of the 5-nucleotide deletion in exon 5 (nucleotides 965 to 969) of the CYP27A1 gene, resulting in a frameshift and insertion of a … (more)
For discussion of the 5-nucleotide deletion in exon 5 (nucleotides 965 to 969) of the CYP27A1 gene, resulting in a frameshift and insertion of a premature codon at position 296, that was found in compound heterozygous state in a patient with cerebrotendinous xanthomatosis by Lamon-Fava et al. (2002), see 606530.0011. (less)
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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 |
Cerebrotendinous xanthomatosis: Possibility of founder mutation in CYP27A1 gene (c.526delG) in Eastern Indian and Surinamese population. | Dutta AK | Molecular genetics and metabolism reports | 2015 | PMID: 26937392 |
Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis. | Lamon-Fava S | Clinical genetics | 2002 | PMID: 12000359 |
Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis. | Verrips A | Brain : a journal of neurology | 2000 | PMID: 10775536 |
Four novel mutations of sterol 27-hydroxylase gene in Italian patients with cerebrotendinous xanthomatosis. | Garuti R | Journal of lipid research | 1997 | PMID: 9392430 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP27A1 | - | - | - | - |
Text-mined citations for rs397515356 ...
HelpRecord last updated May 19, 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.