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Primary immunodeficiency

Gene: NCF4

Green List (high evidence)

NCF4 (neutrophil cytosolic factor 4)
EnsemblGeneIds (GRCh38): ENSG00000100365
EnsemblGeneIds (GRCh37): ENSG00000100365
OMIM: 601488, Gene2Phenotype
NCF4 is in 5 panels

6 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

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Please note 12 additional families reported July 2018.
Created: 12 Jul 2018, 4:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Very strong case for expecting loss of function to be pathogenic
Created: 29 Jun 2018, 2:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified as compound heterozygotes in one case. Supportive in vitro studies of patients' fibroblasts and expression studies of variant mRNA were presented (PMID 19692703).
Created: 2 May 2018, 1:18 p.m.

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
Comment on list classification: Changed Amber to Green from external review comment and further publication to support gene-disease association. van de Geer et al. (July 2018) PMID: 29969437 reported 24 patients from 12 families unrelated with bi-allelic mutations of the NCF4 gene, encoding the NADPH oxidase p40phox protein. Deficiency of p40phox is caused by homozygous (23 patients, 11 families) or compound heterozygous (one patient) mutations in families from eight countries.
Created: 13 Jul 2018, 8:59 a.m.
Comment on publications: Added recent publication suggested from external reviewer to support to Green rating
Created: 13 Jul 2018, 8:43 a.m.
Keep Amber until more info on gene and disease association. Although noted by expert review that this a very strong case for expecting loss of function to be pathogenic- there is currently no compelling functional information to support the rating being green given there is only one reported case to date. Request evidences / immunological association of this gene from GRID, GOSH and Victorian Clinical Genetics Services.
Created: 6 Jul 2018, 4:24 p.m.
Inactivating pathogenic variants in both NCF4 alleles were reported in one individual (PMID:19692703)
Created: 4 Jul 2018, 1:46 p.m.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas.
Created: 4 Jul 2018, 1:32 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NCF4 .PanelApp HGNC gene symbol check: NCF4 . IUIS Disease: Autosomal recessive CGD p40phox . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N + M. IUIS Associated features: Infections, autoinflammatory phenotype. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Defects of Respiratory Burst
Created: 2 Jul 2018, 10:35 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: P40-phox (NCF4), PanelApp HGNC gene symbol check: NCF4, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Chronic granulomatous disease (CGD) / Chronic granulomatous disease (CGD)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: NCF4, GRID_Gene_Symbol: NCF4, GRID_Transcript_ENS_Community submitted: ENST00000397147, GRID_Transcript_RefSeq: NM_013416.3, GRID_Transcript_ENS_used_on_Production: ENST00000397147
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
  • GOSH PID v.8.0
Phenotypes
  • ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III 613960
  • Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III
  • Chronic granulomatous disease (CGD)
  • Infections, autoinflammatory phenotype
  • Congenital defects of phagocyte number or function
OMIM
601488
Clinvar variants
Variants in NCF4
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 NCF4.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to NCF4.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to NCF4.

13 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ncf4 has been classified as Green List (High Evidence).

13 Jul 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: NCF4 were set to 19692703; 29969437

12 Jul 2018, Gel status: 2

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.

6 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ncf4 has been classified as Amber List (Moderate Evidence).

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III 613960, Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III, Chronic granulomatous disease (CGD), Infections, autoinflammatory phenotype, Congenital defects of phagocyte number or function

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to NCF4. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to NCF4. Panel: Primary immunodeficiency disorders

2 May 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NCF4 were set to 19692703

2 May 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III 613960; Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III; Chronic granulomatous disease (CGD)

2 May 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III 613960; Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III; Chronic granulomatous disease (CGD)

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to NCF4. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to NCF4. Panel: Primary immunodeficiency disorders Phenotypes for gene NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III, Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III, Chronic granulomatous disease (CGD)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III, Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to NCF4. Panel: Primary immunodeficiency disorders Phenotypes for gene NCF4 were set to ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III, Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III

6 Apr 2018, Gel status: 1

Clear Sources

Louise Daugherty (Genomics England Curator)

NCF4 Source: GOSH PID 20171173 was removed from gene: NCF4

6 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

GOSH PID v.8.0 was added to NCF4. Panel: Primary immunodeficiency disorders

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

NCF4 was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171173

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

NCF4 was created by Louise Daugherty