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Primary immunodeficiency

Gene: C4B

Green List (high evidence)

C4B (complement C4B (Chido blood group))
EnsemblGeneIds (GRCh38): ENSG00000224389
EnsemblGeneIds (GRCh37): ENSG00000224389
OMIM: 120820, Gene2Phenotype
C4B is in 4 panels

4 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

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

Tracy Briggs (Manchester Genomic Medicine Centre)

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Complete C4 deficiency is associated with susceptibility to invasive infection and SLE
Created: 19 Jun 2018, 6:48 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SLE predisposition

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): C4A+C4B .PanelApp HGNC gene symbol check: C4B . IUIS Disease: Complete C4 deficiency . IUIS Inheritance: AR .T cells: Very low, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A
Created: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease association
Created: 20 Jun 2018, 3:39 p.m.
changed to Green, external expert review notes Complete C4 deficiency is associated with susceptibility to invasive infection and SLE
Created: 20 Jun 2018, 3:39 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.
Created: 20 Jun 2018, 3:38 p.m.
Leave as Amber for external clinical review, conflicting evidence regarding microbial infection
Created: 15 Jun 2018, 4:31 p.m.
Complete or partial C4B deficiencies has been related to vulnerability and severity of microbial infection PMID: 2355198, 12626442, 2788199). However in PMID:19062096 and PMID:1569346 could not confirm this
Created: 15 Jun 2018, 4:25 p.m.
Complete C4 deficiency requires four null alleles and is rarely found, but is highly associated with SLE (75% incidence). Partial C4 deficiencies with one to three null alleles, however, are relatively common, found in up to 25% of individuals. Complete C4A deficiency is greatly over-represented in the SLE population. C4A deficiencies are found in about 1% of the general population and 10–15% of patients with SLE. Complete C4B deficiency has been associated with bacterial infections, suggesting that the functionally of different C4 genes, C4A and C4B contribute differently to host defense and autoimmunity (PMID:2788199, 2355198). However, Cates et al. (1009) PMID:1569346 could not confirm this association, and showed that C4B deficiency is not associated with meningitis or bacteremia with encapsulated bacteria was no increase in homozygous C4B deficiency among patients with bacteremia or meningitis caused by encapsulated bacteria. PMID: 19062096 (2009) no relation was found between C4 isotypic deficiencies and meningitis, in agreement with the results of Cates et al. (1992), but they noted the chort was small.
Created: 15 Jun 2018, 3:54 p.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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: C4B, GRID_Gene_Symbol: C4B, GRID_Transcript_ENS_Community submitted: ENST00000435363, GRID_Transcript_RefSeq: NM_001002029.3, GRID_Transcript_ENS_used_on_Production: ENST00000435363
Created: 17 Apr 2018, 12:12 p.m.

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • GRID V2.0
Phenotypes
  • C4B deficiency, 614379
  • SLE predisposition
  • SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense
  • Complement Deficiencies
OMIM
120820
Clinvar variants
Variants in C4B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to C4B.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to C4B.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to C4B.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene C4B were set to C4B deficiency, 614379, SLE predisposition, SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense, Complement Deficiencies

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to C4B. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to C4B. Panel: Primary immunodeficiency disorders

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c4b has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c4b has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: C4B were set to C4B deficiency, 614379; SLE predisposition

15 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: C4B were set to C4B deficiency, 614379

15 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: C4B were set to 2355198; 12626442; 2788199; 19062096; 1569346

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to C4B. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene C4B were set to C4B deficiency

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

C4B was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

C4B was created by Louise Daugherty