NM_000204.5(CFI):c.355G>A (p.Gly119Arg) AND Macular degeneration, age-related, 13, susceptibility to

Germline classification:: risk factor (1 submission)
Last evaluated:: Jul 1, 2013
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000056257.11

Allele description [Variation Report for NM_000204.5(CFI):c.355G>A (p.Gly119Arg)]

NM_000204.5(CFI):c.355G>A (p.Gly119Arg)

Gene:

CFI:complement factor I [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q25

Genomic location:

Preferred name:

NM_000204.5(CFI):c.355G>A (p.Gly119Arg)

HGVS:

NC_000004.12:g.109764664C>T
NG_007569.1:g.42322G>A
NM_000204.5:c.355G>AMANE SELECT
NM_001318057.2:c.355G>A
NM_001331035.2:c.355G>A
NM_001375278.1:c.355G>A
NM_001375279.1:c.355G>A
NM_001375280.1:c.355G>A
NM_001375281.1:c.355G>A
NM_001375282.1:c.355G>A
NM_001375283.1:c.355G>A
NM_001375284.1:c.-127-2972G>A
NP_000195.2:p.Gly119Arg
NP_000195.3:p.Gly119Arg
NP_001304986.2:p.Gly119Arg
NP_001317964.1:p.Gly119Arg
NP_001362207.1:p.Gly119Arg
NP_001362208.1:p.Gly119Arg
NP_001362209.1:p.Gly119Arg
NP_001362210.1:p.Gly119Arg
NP_001362211.1:p.Gly119Arg
NP_001362212.1:p.Gly119Arg
LRG_48t1:c.355G>A
LRG_48:g.42322G>A
LRG_48p1:p.Gly119Arg
NC_000004.11:g.110685820C>T
NM_000204.3:c.355G>A
NM_000204.4:c.355G>A
NR_164671.1:n.383G>A
NR_164672.1:n.383G>A
NR_164673.1:n.383G>A
P05156:p.Gly119Arg

Protein change:

G119R; GLY119ARG

Links:

UniProtKB: P05156#VAR_063666; OMIM: 217030.0010; dbSNP: rs141853578

NCBI 1000 Genomes Browser:

rs141853578

Molecular consequence:

NM_001375284.1:c.-127-2972G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000204.5:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318057.2:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001331035.2:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375278.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375279.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375280.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375281.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375282.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375283.1:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164671.1:n.383G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164672.1:n.383G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164673.1:n.383G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Macular degeneration, age-related, 13, susceptibility to
Identifiers:: MedGen: C4016436

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000087429	OMIM	no assertion criteria provided	risk factor (Jul 1, 2013)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 23685748, 20513133, 20203157

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000087429

OMIM

no assertion criteria provided

risk factor
(Jul 1, 2013)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A functional variant in the CFI gene confers a high risk of age-related macular degeneration.

van de Ven JP, Nilsson SC, Tan PL, Buitendijk GH, Ristau T, Mohlin FC, Nabuurs SB, Schoenmaker-Koller FE, Smailhodzic D, Campochiaro PA, Zack DJ, Duvvari MR, Bakker B, Paun CC, Boon CJ, Uitterlinden AG, Liakopoulos S, Klevering BJ, Fauser S, Daha MR, Katsanis N, Klaver CC, et al.

Nat Genet. 2013 Jul;45(7):813-7. doi: 10.1038/ng.2640. Epub 2013 May 19.

PubMed [citation]

PMID:: 23685748

Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.

Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ.

Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256.

PubMed [citation]

PMID:: 20513133

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000087429.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In 3 unrelated patients with age-related macular degeneration (ARMD13; 615439), van de Ven et al. (2013) identified heterozygosity for a 355G-A transition in exon 3 of the CFI gene, resulting in a gly119-to-arg (G119R) substitution at a highly conserved residue in the CD5 domain. Genotyping of additional cases resulted in the G119R variant being identified in an overall total of 20 of 3,567 cases versus only 1 of 3,937 controls, consistent with G119R conferring high risk for developing ARMD (odds ratio, 22.20; p = 3.79 x 10(-6)). Van de Ven et al. (2013) noted that most carriers of the G119R variant had stage 4 ARMD. The 1 control carrying the minor allele had numerous hard drusen in all 4 quadrants of the peripheral retina, but had normal macula in both eyes. Van de Ven et al. (2013) also noted that the G119R variant had previously been reported in patients with atypical hemolytic uremic syndrome (AHUS3; 612923) (Maga et al., 2010; Fakhouri et al., 2010); however, there was no significant difference in renal function of ARMD patients with the G119R variant compared to ARMD patients without G119R. Plasma and sera carrying the G119R variant mediated C3b (see 120700) degradation to a lesser extent than that of controls, and the mutant was both expressed and secreted at lower levels in HEK293 cells than wildtype protein. Studies in zebrafish retina demonstrated reduced activity by the G119R mutant in regulating vessel thickness and branching compared to wildtype.

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

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine