VCV000016075.25 - ClinVar

NM_001710.5(CFB):c.95G>A (p.Arg32Gln)

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.

(18)

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/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_001710.5(CFB):c.95G>A (p.Arg32Gln)

Variation ID: 16075 Accession: VCV000016075.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.33 6: 31946403 (GRCh38) [ NCBI UCSC ] 6: 31914180 (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 22, 2016	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001710.6:c.95G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001701.2:p.Arg32Gln	missense
NC_000006.12:g.31946403G>A
NC_000006.11:g.31914180G>A
NG_008191.1:g.5460G>A
NG_011730.1:g.23915G>A
LRG_136:g.5460G>A
LRG_136t1:c.95G>A	LRG_136p1:p.Arg32Gln
LRG_26:g.23915G>A
LRG_26t1:c.*1046G>A
	P00751:p.Arg32Gln

... more HGVS ... less HGVS

Protein change

R32Q

Other names

R8Q

Canonical SPDI

NC_000006.12:31946402:G:A

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.

0.11542 (A)

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

Exome Aggregation Consortium (ExAC) 0.09834

1000 Genomes Project 30x 0.11415

1000 Genomes Project 0.11542

The Genome Aggregation Database (gnomAD) 0.11820

Trans-Omics for Precision Medicine (TOPMed) 0.12273

Links

ClinGen: CA126178 UniProtKB: P00751#VAR_006494 OMIM: 138470.0001 OMIM: 138470.0004 dbSNP: rs641153 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.
C2		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	281	390
CFB		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	439	476

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.
Age related macular degeneration 14	protective (1)	no assertion criteria provided	Aug 12, 2016	RCV000017458.38
BF*FA/S	Benign (1)	no assertion criteria provided	Oct 30, 2017	RCV000017454.37
Factor B fast/slow polymorphism	Benign (1)	no assertion criteria provided	Jan 1, 1994	RCV000017453.11
Complement component 2 deficiency	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000281261.13
Atypical hemolytic-uremic syndrome	Benign (2)	criteria provided, single submitter	Jun 14, 2016	RCV000259759.13
Macular degeneration	Benign/Likely benign (3)	criteria provided, single submitter	Jun 14, 2016	RCV000319518.14
not specified	Benign (3)	criteria provided, single submitter	Mar 28, 2016	RCV000455762.15
Atypical hemolytic-uremic syndrome with B factor anomaly	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV001154197.12
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001515636.17
Focal segmental glomerulosclerosis	Benign (1)	criteria provided, single submitter	Sep 27, 2022	RCV002293980.9
Age related macular degeneration 14 Complement component 2 deficiency	Benign (1)	criteria provided, single submitter	Apr 22, 2022	RCV002504800.8
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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.
Benign (Nov 10, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001745566.1 First in ClinVar: Jul 07, 2021 Last updated: Jul 07, 2021	Comment: This variant is associated with the following publications: (PMID: 28173125, 16518403, 19255449, 21555552, 16936732, 23112567, 18806293)
Benign (Apr 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Complement component 2 deficiency Age related macular degeneration 14 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002796574.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Atypical Hemolytic-Uremic Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462006.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Publications: PubMed (2) PubMed: 16518403‚ 18806293
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Atypical Hemolytic-Uremic Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462001.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Macular Degeneration Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000484213.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Macular Degeneration Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462005.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Macular Degeneration Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462002.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Complement Component C2 Deficiency Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000484214.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538521.1 First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Method: Genome/Exome Filtration
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Atypical hemolytic-uremic syndrome with B factor anomaly Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001315532.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (2) PubMed: 18806293‚ 16518403 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)
Benign (Sep 27, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Inherited focal segmental glomerulosclerosis Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002587291.1 First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022
Benign (Feb 01, 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: SCV001723753.4 First in ClinVar: Jun 15, 2021 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: SCV005225533.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
protective (Aug 12, 2016)	no assertion criteria provided Method: literature only	MACULAR DEGENERATION, AGE-RELATED, 14, REDUCED RISK OF Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037730.4 First in ClinVar: Apr 04, 2013 Last updated: Aug 22, 2016	Publications: PubMed (2) PubMed: 16518403‚ 16936732 Comment on evidence: Gold et al. (2006) identified a 95G-A transition in the CFB gene, resulting in an arg32-to-gln variant (R32Q; rs641153). In approximately 900 individuals with ARMD … (more) Gold et al. (2006) identified a 95G-A transition in the CFB gene, resulting in an arg32-to-gln variant (R32Q; rs641153). In approximately 900 individuals with ARMD (ARMD14; 615489) and approximately 400 controls, they found a significant association between haplotype H7, consisting of the R32Q variant and the intron 10 variant (613927.0005) of the C2 gene, and a reduced risk of ARMD. Maller et al. (2006) replicated the association of the R32Q variant of CFB and the intron 10 variant of C2 with risk of ARMD, noting that although this pair of SNPs has minor alleles that confer an equivalent protective effect, they found these effects to be independent and distinct. (less)
Benign (Oct 30, 2017)	no assertion criteria provided Method: literature only	BF*FA/S Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037726.2 First in ClinVar: Apr 04, 2013 Last updated: Nov 02, 2017	Publications: PubMed (3) PubMed: 6308626‚ 8181962‚ 2249879 Comment on evidence: The molecular basis for allelic variation at the factor B locus, i.e., the 2 common alleles F and S, has been defined; a G-to-A transition … (more) The molecular basis for allelic variation at the factor B locus, i.e., the 2 common alleles F and S, has been defined; a G-to-A transition in codon 8 changes the amino acid from arginine in the S allele to glutamine in the F allele (Campbell, 1987). This fits with the difference in electrophoretic mobility of the 2 variants, with the F allele carrying a less positive charge and thus moving more toward the anode. Mejia et al. (1994) presented the complete cDNA sequence of the BFS allele. BFS is the most common allele. The BFS, BFFA, and BFFB have a combined frequency in excess of 0.95. Davrinche et al. (1990) showed that these differ from one another at the codon for the seventh amino acid: CAG (gln) in BFFA, TGG (trp) in BFFB, and CGG (arg) in BFS. The changes involve nucleotides 94 and 95 (see fig. 1 of Mejia et al., 1994). (Codon 8 in the cDNA corresponds to amino acid 7 in the protein.) (less)
Benign (Jan 01, 1994)	no assertion criteria provided Method: literature only	FACTOR B FAST-SLOW POLYMORPHISM Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037725.2 First in ClinVar: Apr 04, 2013 Last updated: Nov 02, 2017	Publications: PubMed (3) PubMed: 6308626‚ 8181962‚ 2249879 Comment on evidence: The molecular basis for allelic variation at the factor B locus, i.e., the 2 common alleles F and S, has been defined; a G-to-A transition … (more) The molecular basis for allelic variation at the factor B locus, i.e., the 2 common alleles F and S, has been defined; a G-to-A transition in codon 8 changes the amino acid from arginine in the S allele to glutamine in the F allele (Campbell, 1987). This fits with the difference in electrophoretic mobility of the 2 variants, with the F allele carrying a less positive charge and thus moving more toward the anode. Mejia et al. (1994) presented the complete cDNA sequence of the BFS allele. BFS is the most common allele. The BFS, BFFA, and BFFB have a combined frequency in excess of 0.95. Davrinche et al. (1990) showed that these differ from one another at the codon for the seventh amino acid: CAG (gln) in BFFA, TGG (trp) in BFFB, and CGG (arg) in BFS. The changes involve nucleotides 94 and 95 (see fig. 1 of Mejia et al., 1994). (Codon 8 in the cDNA corresponds to amino acid 7 in the protein.) (less)
Benign (-)	no assertion criteria provided Method: clinical testing	not specified 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: SCV001931346.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified 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: SCV001958716.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

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.

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
Analysis of rare variants in the complement component 2 (C2) and factor B (BF) genes refine association for age-related macular degeneration (AMD).	Richardson AJ	Investigative ophthalmology & visual science	2009	PMID: 18806293
Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.	Maller J	Nature genetics	2006	PMID: 16936732
Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.	Gold B	Nature genetics	2006	PMID: 16518403
Human factor B. Complete cDNA sequence of the BF*S allele.	Mejía JE	Human immunology	1994	PMID: 8181962
Molecular characterization of human complement factor B subtypes.	Davrinche C	Immunogenetics	1990	PMID: 2249879
Molecular cloning and characterization of the gene coding for human complement protein factor B.	Campbell RD	Proceedings of the National Academy of Sciences of the United States of America	1983	PMID: 6308626

Text-mined citations for rs641153 ...

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 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001710.5(CFB):c.95G>A (p.Arg32Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs641153 ...