NM_000186.4(CFH):c.2488C>T (p.Arg830Trp) AND Factor H deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003448434.3

Allele description [Variation Report for NM_000186.4(CFH):c.2488C>T (p.Arg830Trp)]

NM_000186.4(CFH):c.2488C>T (p.Arg830Trp)

Gene:

CFH:complement factor H [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_000186.4(CFH):c.2488C>T (p.Arg830Trp)

HGVS:

NC_000001.11:g.196736898C>T
NG_007259.1:g.89888C>T
NM_000186.4:c.2488C>TMANE SELECT
NP_000177.2:p.Arg830Trp
LRG_47:g.89888C>T
NC_000001.10:g.196706028C>T

Protein change:

R830W

Links:

dbSNP: rs62641696

NCBI 1000 Genomes Browser:

rs62641696

Molecular consequence:

NM_000186.4:c.2488C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Factor H deficiency (CFHD)
Synonyms:: COMPLEMENT FACTOR H DEFICIENCY; CFH DEFICIENCY
Identifiers:: MONDO: MONDO:0012350; MedGen: C0398777; OMIM: 609814

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004176619	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004177317	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004176619

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 14, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004177317

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004176619.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The missense c.2488C>T (p.Arg830Trp) variant in CFH gene has been reported previously in individuals affected with C3-glomerulopathy / atypical hemolytic uremic syndrome (Merinero et al. 2017; Geerlings et al. 2018). The p.Arg830Trp is reported with an allele frequency of 0.007% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain_significance with a status of criteria provided, single submitter. The amino acid change p.Arg830Trp in CFH is predicted as conserved by GERP++. The amino acid Arg at position 830 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004177317.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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