Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CFB

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Susceptibility to atypical haemolytic uraemic syndrome (4; AD); complement factor B deficiency (AR)

I don't know

OriginaI Metadata from IUIS classification table (December, 2019). IUIS Genetic defect (original gene symbol in IUIS download): CFB .PanelApp HGNC gene symbol check: CFB . IUIS Disease: Factor B . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Atypical Hemolytic-uremic syndrome. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CFB .PanelApp HGNC gene symbol check: CFB . IUIS Disease: Factor B . IUIS Inheritance: AD GOF / AR .T cells: Normal / Normal , .B cells: Normal / Normal, Immunoglobulin levels:Normal / Normal, Neutrophil count: Normal / Normal .IUIS Other affected cells: N/A. IUIS Associated features: Infections with encapsulated organisms. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A.

Created: 28 Feb 2020, 4:32 p.m. | Last Modified: 28 Feb 2020, 4:37 p.m.

Panel Version: 2.27

Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber.

Created: 12 Nov 2019, 5:01 p.m. | Last Modified: 12 Nov 2019, 5:01 p.m.

Panel Version: 1.137

?Complement factor B deficiency: one family, relevant phenotype - ?amber

Created: 26 Sep 2019, 3:51 p.m. | Last Modified: 26 Sep 2019, 3:51 p.m.

Panel Version: 1.130

This is a relevant phenotype but there is not enough evidence in the literature to date (one case) and there has been no further evidence in terms of unpublished cases other than a Green rating recommendation from the Immunology Specialist Test Group. To remain Amber unless further supporting evidence from the Test Group

Created: 17 Sep 2019, 4:50 p.m. | Last Modified: 17 Sep 2019, 4:50 p.m.

Panel Version: 1.95

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

One family reported, therefore left Amber until further evidence to support Green rating by external expert

Created: 11 Jul 2018, 4:11 p.m.

Comment on phenotypes: added phenotypes and specific MOI as suggested by expert review

Created: 2 Jul 2018, 3:50 p.m.

Comment on mode of inheritance: changed MOI from expert review and review of IUIS data

Created: 2 Jul 2018, 3:49 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CFB .PanelApp HGNC gene symbol check: CFB . IUIS Disease: Factor B . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Atypical Hemolytic-uremic syndrome. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CFB .PanelApp HGNC gene symbol check: CFB . IUIS Disease: Factor B . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Infections with encapsulated organisms. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A.

Created: 2 Jul 2018, 10:50 a.m.

Currently only one report of this deficiency in humans, reviewed and decided to keep amber until more info on gene and disease association.

Created: 11 Jun 2018, 9:06 a.m.

Comment on publications: Added publication Slade et al. (2013) PMID:2415220. Only one affected (1 family) reported to date in which a 32-year-old woman, born of unrelated parents of English and Scottish origin, with complement factor B deficiency (CFBD; 615561) manifest as recurrent systemic infections with encapsulated bacteria since early childhood, Slade et al. (2013) identified compound heterozygous mutations in the CFB gene: a c.766C-T transition in exon 6, resulting in a gln256-to-ter (Q256X) substitution, and a 4-bp deletion (c.1894_1987delTTTG; 138470.0008) in exon 15, resulting in a frameshift and premature termination (Phe632CysfsTer8). Laboratory studies showed normal immunoglobulins and lymphocytes, but functional ELISA showed that the alternative complement pathway was inactive. The defect was not complemented by factor B-depleted serum, and factor B was undetectable by radial immunodiffusion. The mutations were found by genome sequencing of the CFB gene and segregated with the disorder in the family.

Created: 11 Jun 2018, 9:03 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: Factor B, PanelApp HGNC gene symbol check: CFB, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement factor B deficiency

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CFB, GRID_Gene_Symbol: CFB, GRID_Transcript_ENS_Community submitted: ENST00000425368, GRID_Transcript_RefSeq: NM_001710.5, GRID_Transcript_ENS_used_on_Production: ENST00000425368

Created: 17 Apr 2018, 12:12 p.m.