NM_000204.5(CFI):c.1547G>T (p.Gly516Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001967578.5

Allele description [Variation Report for NM_000204.5(CFI):c.1547G>T (p.Gly516Val)]

NM_000204.5(CFI):c.1547G>T (p.Gly516Val)

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.1547G>T (p.Gly516Val)

HGVS:

NC_000004.12:g.109741098C>A
NG_007569.1:g.65888G>T
NM_000204.5:c.1547G>TMANE SELECT
NM_001318057.2:c.1571G>T
NM_001331035.2:c.1526G>T
NM_001375278.1:c.1558+1393G>T
NM_001375279.1:c.1534+1393G>T
NM_001375280.1:c.1513+1393G>T
NM_001375281.1:c.1534+1393G>T
NM_001375282.1:c.1513+1393G>T
NM_001375283.1:c.1490G>T
NM_001375284.1:c.938G>T
NP_000195.3:p.Gly516Val
NP_001304986.2:p.Gly524Val
NP_001317964.1:p.Gly509Val
NP_001362212.1:p.Gly497Val
NP_001362213.1:p.Gly313Val
LRG_48:g.65888G>T
NC_000004.11:g.110662254C>A
NR_164671.1:n.1294G>T
NR_164672.1:n.1597G>T
NR_164673.1:n.1571G>T

Protein change:

G313V

Links:

dbSNP: rs764347930

NCBI 1000 Genomes Browser:

rs764347930

Molecular consequence:

NM_001375278.1:c.1558+1393G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001375279.1:c.1534+1393G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001375280.1:c.1513+1393G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001375281.1:c.1534+1393G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001375282.1:c.1513+1393G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000204.5:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318057.2:c.1571G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001331035.2:c.1526G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375283.1:c.1490G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375284.1:c.938G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_164671.1:n.1294G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164672.1:n.1597G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164673.1:n.1571G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV002213448	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29566171, 33609329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002213448

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2024)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic analysis of the complement pathway in C3 glomerulopathy.

Zhao W, Ding Y, Lu J, Zhang T, Chen D, Zhang H, Zeng C, Liu Z, Chen H.

Nephrol Dial Transplant. 2018 Nov 1;33(11):1919-1927. doi: 10.1093/ndt/gfy033.

PubMed [citation]

PMID:: 29566171

Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: A Swedish retrospective observational study.

Åkesson A, Martin M, Blom AM, Rossing M, Gabrielaite M, Zetterberg E, Klintman J.

Ther Apher Dial. 2021 Dec;25(6):988-1000. doi: 10.1111/1744-9987.13634. Epub 2021 Mar 31.

PubMed [citation]

PMID:: 33609329

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002213448.2

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 516 of the CFI protein (p.Gly516Val). This variant is present in population databases (rs764347930, gnomAD 0.05%). This missense change has been observed in individual(s) with C3 glomerulopathy and/or hemolytic uremic syndrome (PMID: 29566171, 33609329). ClinVar contains an entry for this variant (Variation ID: 1431614). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFI protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine