VCV000039267.27 - ClinVar

NM_207352.4(CYP4V2):c.64C>G (p.Leu22Val)

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.

(16)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_207352.4(CYP4V2):c.64C>G (p.Leu22Val)

Variation ID: 39267 Accession: VCV000039267.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q35.1 4: 186191887 (GRCh38) [ NCBI UCSC ] 4: 187113041 (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	May 3, 2013	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_207352.4:c.64C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_997235.3:p.Leu22Val	missense
NC_000004.12:g.186191887C>G
NC_000004.11:g.187113041C>G
NG_007965.1:g.5368C>G
	Q6ZWL3:p.Leu22Val

... more HGVS ... less HGVS

Protein change

L22V

Other names

c.367C>G

Canonical SPDI

NC_000004.12:186191886:C:G

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.

0.40974 (G)

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

1000 Genomes Project 0.40974

1000 Genomes Project 30x 0.41537

The Genome Aggregation Database (gnomAD), exomes 0.44357

Trans-Omics for Precision Medicine (TOPMed) 0.45273

The Genome Aggregation Database (gnomAD) 0.46276

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.46360

Exome Aggregation Consortium (ExAC) 0.52893

Links

dbSNP: rs1055138 ClinGen: CA149664 UniProtKB: Q6ZWL3#VAR_038606 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.
CYP4V2		-	-	GRCh38 GRCh37	449	703
LOC129993526	-	-	-	GRCh38	-	88

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	Benign (4)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000132719.17
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Jul 25, 2013	RCV000082840.23
Corneal dystrophy	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000278726.13
Bietti crystalline corneoretinal dystrophy	Benign (6)	criteria provided, multiple submitters, no conflicts	Jul 30, 2021	RCV000032544.22
Retinal dystrophy	Benign (1)	criteria provided, single submitter	Oct 1, 2023	RCV003887878.1

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.
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Bietti crystalline corneoretinal dystrophy Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136794.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001726720.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (Nov 20, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bietti crystalline corneoretinal dystrophy Affected status: no Allele origin: germline	Molecular Genetics, Royal Melbourne Hospital Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002503667.2 First in ClinVar: Apr 30, 2022 Last updated: Apr 15, 2024	Comment: Population allele frequency is 45% (101,504/227,310 alleles; gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following … (more) Population allele frequency is 45% (101,504/227,310 alleles; gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000317259.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jul 25, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000114892.8 First in ClinVar: Jan 17, 2014 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP4V2 Number of individuals with the variant: 18 Zygosity: Homozygote, Single Heterozygote Sex: mixed
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Bietti crystalline corneoretinal dystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000448813.3 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)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Corneal dystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000448814.3 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)
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bietti crystalline corneoretinal dystrophy Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001876505.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Mar 14, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001899699.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Oct 01, 2023)	criteria provided, single submitter (Submitter's publication) Method: research	Retinal dystrophy Affected status: yes Allele origin: germline	Dept Of Ophthalmology, Nagoya University Accession: SCV004706571.1 First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005306602.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
probable-non-pathogenic (-)	no assertion criteria provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	Department of Ophthalmology and Visual Sciences Kyoto University Accession: SCV000172673.1 First in ClinVar: Aug 08, 2014 Last updated: Aug 08, 2014	Comment: Converted during submission to Likely benign.
Benign (-)	no assertion criteria provided Method: clinical testing	Bietti crystalline corneoretinal dystrophy Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734333.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001921231.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
pathologic (Apr 12, 2012)	no assertion criteria provided Method: curation	Bietti Crystalline Dystrophy Affected status: not provided Allele origin: not provided	GeneReviews Accession: SCV000056211.2 First in ClinVar: Apr 04, 2013 Last updated: May 03, 2013	Comment: Converted during submission to Pathogenic.
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	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: SCV001957091.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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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 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.

Comment:

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
Bietti Crystalline Dystrophy.	Adam MP	-	2019	PMID: 22497028
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP4V2	-	-	-	-

Text-mined citations for rs1055138 ...

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 Dec 15, 2024

ClinVar Genomic variation as it relates to human health

NM_207352.4(CYP4V2):c.64C>G (p.Leu22Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1055138 ...