ClinVar Genomic variation as it relates to human health
NM_001395413.1(POR):c.1707G>A (p.Ser569=)
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_001395413.1(POR):c.1707G>A (p.Ser569=)
Variation ID: 256841 Accession: VCV000256841.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q11.23 7: 75985969 (GRCh38) [ NCBI UCSC ] 7: 75615287 (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 3, 2016 Sep 29, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001395413.1:c.1707G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001382342.1:p.Ser569= synonymous NM_001367562.3:c.1707G>A NP_001354491.2:p.Ser569= synonymous NM_001382655.3:c.1761G>A NP_001369584.2:p.Ser587= synonymous NM_001382657.2:c.1707G>A NP_001369586.2:p.Ser569= synonymous NM_001382658.3:c.1707G>A NP_001369587.2:p.Ser569= synonymous NM_001382659.3:c.1707G>A NP_001369588.2:p.Ser569= synonymous NM_001382662.3:c.1557G>A NP_001369591.2:p.Ser519= synonymous NC_000007.14:g.75985969G>A NC_000007.13:g.75615287G>A NG_008930.1:g.75868G>A NW_003871064.1:g.3515205G>A - Protein change
- Other names
- -
- Canonical SPDI
- NC_000007.14:75985968:G:A
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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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0.19529 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.19425
1000 Genomes Project 0.19529
Trans-Omics for Precision Medicine (TOPMed) 0.26652
The Genome Aggregation Database (gnomAD), exomes 0.27955
The Genome Aggregation Database (gnomAD) 0.28425
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.28530
Exome Aggregation Consortium (ExAC) 0.38105
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
Help
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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POR | - | - |
GRCh38 GRCh37 |
719 | 861 |
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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Benign (3) |
criteria provided, single submitter
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- | RCV000243975.21 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000356109.22 | |
Benign (1) |
criteria provided, single submitter
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- | RCV001292551.10 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2023 | RCV001706299.20 |
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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Benign
(-)
|
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: SCV000305588.1
First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016 |
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000470032.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Nov 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604907.10
First in ClinVar: Oct 03, 2016 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: case-control
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Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Affected status: yes, no
Allele origin:
germline
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Pecori Giraldi Lab, University of Milan
Accession: SCV001432707.1
First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021 |
Observation 1: Observation 2: |
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001833135.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001718393.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024 |
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Benign
(Jun 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557956.2
First in ClinVar: Aug 08, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Benign. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with disordered steroidogenesis due to cytochrome P450 oxidoreductase (MIM#613571) and Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (MIM#201750). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (I) 0252 - This variant is homozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of disordered steroidogenesis due to cytochrome P450 oxidoreductase (MIM#613571) and Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (MIM#201750) (gnomAD v2: 44162 heterozygotes, 10290 homozygotes). (SB) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. (SB) 0600 - Variant is located in the annotated oxidoreductase NAD-binding domain (DECIPHER). (I) 0705 - No comparable single nucleotide substitution variants have previous evidence for pathogenicity. (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. It has frequently been reported as benign or a polymorphism, including in individuals with POH or 21 hydroxylase deficiency (ClinVar, PMIDs: 27376429, 33666875). (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005264870.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
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: SCV001739583.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952474.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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POR polymorphisms are associated with 21 hydroxylase deficiency. | Pecori Giraldi F | Journal of endocrinological investigation | 2021 | PMID: 33666875 |
P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms. | Burkhard FZ | The Journal of steroid biochemistry and molecular biology | 2017 | PMID: 27068427 |
Delayed diagnosis of disorder of sex development (DSD) due to P450 oxidoreductase (POR) deficiency. | Koika V | Hormones (Athens, Greece) | 2016 | PMID: 27376429 |
Pharmacogenomics of human P450 oxidoreductase. | Pandey AV | Frontiers in pharmacology | 2014 | PMID: 24847272 |
Consequences of POR mutations and polymorphisms. | Miller WL | Molecular and cellular endocrinology | 2011 | PMID: 21070833 |
Text-mined citations for rs1057870 ...
HelpRecord last updated Oct 08, 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.