This variant is associated with the following publications: (PMID: 21106043, 25087612, 20538655, 23274582, 18340363, 19549636, 18421087, 20574013, 24722444, 21270465, 24550392, 22509112, 23441108, 20132989, 19187823, 21397333, 21555552, 16299065, 29686068, 28173125)
ClinVar Genomic variation as it relates to human health
NM_000186.4(CFH):c.184G>A (p.Val62Ile)
Germline
Classification
Help
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.
(15)
Help
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
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000186.4(CFH):c.184G>A (p.Val62Ile)
Variation ID: 16550 Accession: VCV000016550.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q31.3 1: 196673103 (GRCh38) [ NCBI UCSC ] 1: 196642233 (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 Aug 13, 2015 Sep 29, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000186.4:c.184G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000177.2:p.Val62Ile missense NM_001014975.3:c.184G>A NP_001014975.1:p.Val62Ile missense NC_000001.11:g.196673103G>A NC_000001.10:g.196642233G>A NG_007259.1:g.26093G>A LRG_47:g.26093G>A LRG_47t1:c.184G>A LRG_47p1:p.Val62Ile - Protein change
- V62I
- Other names
-
CFH, ILE62VAL (rs800292)
I62V
- Canonical SPDI
- NC_000001.11:196673102: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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0.46805 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.31738
Exome Aggregation Consortium (ExAC) 0.32095
The Genome Aggregation Database (gnomAD) 0.40446
Trans-Omics for Precision Medicine (TOPMed) 0.41746
1000 Genomes Project 0.46805
1000 Genomes Project 30x 0.46924
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| CFH | - | - |
GRCh38 GRCh38 GRCh37 |
833 | 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. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 22, 2021 | RCV000018017.11 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000190297.10 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 22, 2021 | RCV000274380.8 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 22, 2021 | RCV000374816.7 | |
| Benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000331871.5 | |
| Benign (1) |
criteria provided, single submitter
|
Jul 22, 2021 | RCV001579191.2 | |
| Benign (1) |
criteria provided, single submitter
|
Sep 27, 2022 | RCV002293982.2 |
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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|---|---|---|---|---|---|
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Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Basal laminar drusen
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001135487.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
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Benign
(May 04, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001950713.2
First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 21106043, 25087612, 20538655, 23274582, 18340363, 19549636, 18421087, 20574013, 24722444, 21270465, 24550392, 22509112, 23441108, 20132989, 19187823, 21397333, … (more)
This variant is associated with the following publications: (PMID: 21106043, 25087612, 20538655, 23274582, 18340363, 19549636, 18421087, 20574013, 24722444, 21270465, 24550392, 22509112, 23441108, 20132989, 19187823, 21397333, 21555552, 16299065, 29686068, 28173125) (less)
|
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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Age related macular degeneration 4
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000352351.3
First in ClinVar: Dec 06, 2016 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
|
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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Basal laminar drusen
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000352348.3
First in ClinVar: Dec 06, 2016 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Membranoproliferative glomerulonephritis with complement factor h deficiency
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000352349.3
First in ClinVar: Dec 06, 2016 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
|
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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hemolytic uremic syndrome, atypical, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000352350.3
First in ClinVar: Dec 06, 2016 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Factor H deficiency
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001806631.1
First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
Sex: mixed
|
|
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Benign
(Jul 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Basal laminar drusen
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001806630.1
First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
Sex: mixed
|
|
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Benign
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Age related macular degeneration 4
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001806633.1
First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
Sex: mixed
|
|
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Benign
(Jul 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hemolytic uremic syndrome, atypical, susceptibility to, 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001806632.1
First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
Sex: mixed
|
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Benign
(Sep 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Inherited focal segmental glomerulosclerosis
Affected status: unknown
Allele origin:
germline
|
Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002587286.1
First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022 |
|
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001730978.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
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Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005285375.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
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risk factor
(Sep 11, 2011)
|
no assertion criteria provided
Method: literature only
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MACULAR DEGENERATION, AGE-RELATED, 4, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000038296.4
First in ClinVar: Apr 04, 2013 Last updated: Jun 14, 2019 |
Comment on evidence:
Hageman et al. (2005) found significant association between an ile62-to-val (I62V; rs800292) variant in the CFH gene and age-related macular degeneration (ARMD4; 610698) among 954 … (more)
Hageman et al. (2005) found significant association between an ile62-to-val (I62V; rs800292) variant in the CFH gene and age-related macular degeneration (ARMD4; 610698) among 954 patients. In 2 subsets of the cases, the I62V allele conferred increased odds ratio for disease development of 2.79 and 1.95, respectively. Hageman et al. (2005) stated that the I62V variant is located in exon 2 within a region that includes a C3b (120700)-binding site. By structural analysis, Hocking et al. (2008) determined that the I62V mutation caused rearrangements within the core of CFH module-1 and increased thermal stability. In a matched sample set from the Age-Related Eye Disease Study (AREDS) cohort involving 424 patients with ARMD and 215 patients without ARMD acting as controls, Bergeron-Sawitzke et al. (2009) confirmed association between ARMD and the GG genotype of rs800292 (OR, 3.7; p = 8.0 x 10(-4)). To identify genetic factors that modify the risk of exudative ARMD in the Japanese population, Arakawa et al. (2011) conducted a genomewide association study and a replication study using a total of 1,536 individuals with exudative AMD and 18,894 controls. Arakawa et al. (2011) confirmed association of the rs800292 SNP in CFH (p = 4.23 x 10(-15)). (less)
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Department of Ophthalmology and Visual Sciences Kyoto University
Accession: SCV000196520.1
First in ClinVar: Aug 13, 2015 Last updated: Aug 13, 2015 |
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Comment:
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
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:
This variant is associated with the following publications: (PMID: 21106043, 25087612, 20538655, 23274582, 18340363, 19549636, 18421087, 20574013, 24722444, 21270465, 24550392, 22509112, 23441108, 20132989, 19187823, 21397333, 21555552, 16299065, 29686068, 28173125)
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population. | Arakawa S | Nature genetics | 2011 | PMID: 21909106 |
| Multilocus analysis of age-related macular degeneration. | Bergeron-Sawitzke J | European journal of human genetics : EJHG | 2009 | PMID: 19259132 |
| Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations. | Hocking HG | The Journal of biological chemistry | 2008 | PMID: 18252712 |
| A function retained by the common mutant CLN3 protein is responsible for the late onset of juvenile neuronal ceroid lipofuscinosis. | Kitzmüller C | Human molecular genetics | 2008 | PMID: 17947292 |
| Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). | Abrera-Abeleda MA | Journal of medical genetics | 2006 | PMID: 16299065 |
| A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. | Hageman GS | Proceedings of the National Academy of Sciences of the United States of America | 2005 | PMID: 15870199 |
| Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. | Nicolaides NC | Nature | 1994 | PMID: 8072530 |
Text-mined citations for rs800292 ...
HelpThese 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 Sep 29, 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.