VCV000065580.32 - ClinVar

NM_000204.5(CFI):c.782G>A (p.Gly261Asp)

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.

(11)

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.

Likely 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_000204.5(CFI):c.782G>A (p.Gly261Asp)

Variation ID: 65580 Accession: VCV000065580.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q25 4: 109760371 (GRCh38) [ NCBI UCSC ] 4: 110681527 (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	Oct 3, 2013	Oct 20, 2024	Jan 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000204.5:c.782G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000195.3:p.Gly261Asp	missense
NM_001318057.2:c.782G>A	NP_001304986.2:p.Gly261Asp	missense
NM_001331035.2:c.782G>A	NP_001317964.1:p.Gly261Asp	missense
NM_001375278.1:c.782G>A	NP_001362207.1:p.Gly261Asp	missense
NM_001375279.1:c.782G>A	NP_001362208.1:p.Gly261Asp	missense
NM_001375280.1:c.782G>A	NP_001362209.1:p.Gly261Asp	missense
NM_001375281.1:c.782G>A	NP_001362210.1:p.Gly261Asp	missense
NM_001375282.1:c.782G>A	NP_001362211.1:p.Gly261Asp	missense
NM_001375283.1:c.782G>A	NP_001362212.1:p.Gly261Asp	missense
NM_001375284.1:c.173G>A	NP_001362213.1:p.Gly58Asp	missense
NR_164671.1:n.810G>A		non-coding transcript variant
NR_164672.1:n.810G>A		non-coding transcript variant
NR_164673.1:n.810G>A		non-coding transcript variant
NC_000004.12:g.109760371C>T
NC_000004.11:g.110681527C>T
NG_007569.1:g.46615G>A
LRG_48:g.46615G>A
LRG_48t1:c.782G>A

... more HGVS ... less HGVS

Protein change

G261D, G58D

Other names

Canonical SPDI

NC_000004.12:109760370:C:T

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.

0.00040 (T)

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

1000 Genomes Project 30x 0.00031

1000 Genomes Project 0.00040

Exome Aggregation Consortium (ExAC) 0.00133

The Genome Aggregation Database (gnomAD), exomes 0.00136

The Genome Aggregation Database (gnomAD) 0.00153

Trans-Omics for Precision Medicine (TOPMed) 0.00153

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00169

Links

ClinGen: CA344907 dbSNP: rs112534524 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.
CFI		-	-	GRCh38 GRCh37	502	515

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.
Atypical hemolytic-uremic syndrome with I factor anomaly	Likely benign (2)	criteria provided, single submitter	Apr 27, 2017	RCV000055784.7
not provided	Likely benign (5)	criteria provided, multiple submitters, no conflicts	Jan 29, 2024	RCV000892174.21
Chronic kidney disease	Likely benign (1)	criteria provided, single submitter	May 28, 2020	RCV001171354.1
CFI-related disorder	Likely benign (1)	no assertion criteria provided	Jun 7, 2023	RCV004537251.2
Atypical hemolytic-uremic syndrome	Likely benign (1)	criteria provided, single submitter	Jan 5, 2021	RCV002294012.2
Age related macular degeneration 13 Atypical hemolytic-uremic syndrome with I factor anomaly Factor I deficiency	Likely benign (1)	criteria provided, single submitter	Apr 6, 2022	RCV002496740.1

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.
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Atypical hemolytic-uremic syndrome with I factor anomaly Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000446883.3 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (May 28, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Chronic kidney disease (Autosomal dominant inheritance) Affected status: yes Allele origin: unknown	Cavalleri Lab, Royal College of Surgeons in Ireland Accession: SCV001328301.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: PP3, BP6, BS1
Likely benign (Jan 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Atypical hemolytic-uremic syndrome Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002587674.1 First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022
Likely benign (Jan 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: SCV004148684.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: CFI: BP4 Number of individuals with the variant: 3
Likely benign (Apr 06, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Factor I deficiency Atypical hemolytic-uremic syndrome with I factor anomaly Age related macular degeneration 13 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002810046.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Likely benign (Jan 29, 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: SCV001036036.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Likely 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: SCV005263061.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided 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: SCV001952346.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Likely benign (Jun 07, 2023)	no assertion criteria provided Method: clinical testing	CFI-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004749183.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001927386.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
not provided (-)	no classification provided Method: literature only	Atypical hemolytic-uremic syndrome with I factor anomaly Affected status: not provided Allele origin: unknown	GeneReviews Accession: SCV000086750.2 First in ClinVar: Oct 03, 2013 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 17084897‚ 20301541 BookShelf: NBK1367 BookShelf: NBK1367
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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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely 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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genetic Atypical Hemolytic-Uremic Syndrome.	Adam MP	-	2021	PMID: 20301541
A mutation in factor I that is associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation.	Nilsson SC	Molecular immunology	2007	PMID: 17084897

Text-mined citations for rs112534524 ...

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 Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_000204.5(CFI):c.782G>A (p.Gly261Asp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs112534524 ...