VCV000284175.51 - ClinVar

NM_001395413.1(POR):c.1882G>A (p.Val628Ile)

Germline

Classification

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.

(10)

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.

Conflicting classifications of pathogenicity
Uncertain significance(3); Benign(1); Likely benign(3)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001395413.1(POR):c.1882G>A (p.Val628Ile)

Variation ID: 284175 Accession: VCV000284175.51

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q11.23 7: 75986234 (GRCh38) [ NCBI UCSC ] 7: 75615552 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 6, 2016	Oct 20, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001395413.1:c.1882G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001382342.1:p.Val628Ile	missense
NM_001367562.3:c.1882G>A	NP_001354491.2:p.Val628Ile	missense
NM_001382655.3:c.1936G>A	NP_001369584.2:p.Val646Ile	missense
NM_001382657.2:c.1882G>A	NP_001369586.2:p.Val628Ile	missense
NM_001382658.3:c.1882G>A	NP_001369587.2:p.Val628Ile	missense
NM_001382659.3:c.1882G>A	NP_001369588.2:p.Val628Ile	missense
NM_001382662.3:c.1732G>A	NP_001369591.2:p.Val578Ile	missense
NC_000007.14:g.75986234G>A
NC_000007.13:g.75615552G>A
NG_008930.1:g.76133G>A

... more HGVS ... less HGVS

Protein change

V578I, V628I, V646I

Other names

Canonical SPDI

NC_000007.14:75986233:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00240 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00106

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00128

Trans-Omics for Precision Medicine (TOPMed) 0.00143

The Genome Aggregation Database (gnomAD), exomes 0.00166

Exome Aggregation Consortium (ExAC) 0.00174

1000 Genomes Project 30x 0.00219

1000 Genomes Project 0.00240

Links

ClinGen: CA4304330 dbSNP: rs145782750 VarSome

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
Gene	OMIM	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.
POR		-	-	GRCh38 GRCh37	720	862

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.
not provided	Conflicting interpretations of pathogenicity (6)	criteria provided, conflicting classifications	Feb 1, 2024	RCV000353254.43
Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Jan 30, 2024	RCV001088190.21
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis	Uncertain significance (1)	criteria provided, single submitter	Feb 26, 2020	RCV001786353.9
POR-related disorder	Uncertain significance (1)	no assertion criteria provided	Apr 17, 2024	RCV004737412.1

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.
Uncertain significance (Nov 05, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000336691.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=POR Number of individuals with the variant: 3 Sex: mixed
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001326421.1 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Likely benign (Mar 27, 2020)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001471857.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021
Likely benign (Apr 22, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001813942.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Comment: This variant is associated with the following publications: (PMID: 25712184, 27068427, 27032764, 27884173, 16467261, 17635179, 18551037, 15793702, 20732302, 28731962)
Uncertain significance (Feb 26, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis Affected status: unknown Allele origin: germline	Centogene AG - the Rare Disease Company Accession: SCV002028312.1 First in ClinVar: Dec 04, 2021 Last updated: Dec 04, 2021
Benign (Jan 30, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001020803.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024
Likely benign (Feb 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001155092.27 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Comment: POR: BS2 Number of individuals with the variant: 7
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	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: SCV001979788.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001980009.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
Uncertain significance (Apr 17, 2024)	no assertion criteria provided Method: clinical testing	POR-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005353241.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The POR c.1891G>A variant is predicted to result in the amino acid substitution p.Val631Ile. This variant was reported in individuals with POR deficiency (Miller et … (more) The POR c.1891G>A variant is predicted to result in the amino acid substitution p.Val631Ile. This variant was reported in individuals with POR deficiency (Miller et al. 2005. PubMed ID: 16467261; Agrawal et al. 2008. PubMed ID: 18551037; Pandey et al. 2010. PubMed ID: 20732302; Flück et al. 2016. PubMed ID: 27032764; Abouelhoda et al. 2016. PubMed ID: 27884173; Kars et al. 2021. PubMed ID: 34426522). This variant is reported in 0.40% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)

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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Comment:

The POR c.1891G>A variant is predicted to result in the amino acid substitution p.Val631Ile. This variant was reported in individuals with POR deficiency (Miller et al. 2005. PubMed ID: 16467261; Agrawal et al. 2008. PubMed ID: 18551037; Pandey et al. 2010. PubMed ID: 20732302; Flück et al. 2016. PubMed ID: 27032764; Abouelhoda et al. 2016. PubMed ID: 27884173; Kars et al. 2021. PubMed ID: 34426522). This variant is reported in 0.40% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=POR	-	-	-	-

Text-mined citations for rs145782750 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 27, 2024

ClinVar Genomic variation as it relates to human health

NM_001395413.1(POR):c.1882G>A (p.Val628Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs145782750 ...