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Intellectual disability
Gene: NFIB

NFIB (nuclear factor I B)
EnsemblGeneIds (GRCh38): ENSG00000147862
EnsemblGeneIds (GRCh37): ENSG00000147862
OMIM: 600728, Gene2Phenotype
NFIB is in 4 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

Comment on list classification: The patients reported in PMID:30388402 presented with borderline-mild intellectual disability. The severity of ID/ GDD was not reported for the single patient with NFIB variant from PMID:39567597. Hence, the rating should still remain amber with current evidence.
Created: 4 Feb 2025, 5:08 p.m. | Last Modified: 4 Feb 2025, 5:08 p.m.

Panel Version: 8.72

Comment on publications: PMID:39567597 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 4 Feb 2025, 5:04 p.m. | Last Modified: 4 Feb 2025, 5:04 p.m.

Panel Version: 8.71

PMID:39567597 reported a study analysing 58 patients with undiagnosed disorders. One of them was identified with a likely pathogenic variant bin NFIB gene (p.G234fs). The patient was reported with global developmental delay and intellectual disability and severity of these are not reported in the publication.
Created: 4 Feb 2025, 5:01 p.m. | Last Modified: 4 Feb 2025, 5:01 p.m.

Panel Version: 8.67

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Macrocephaly, acquired, with impaired intellectual development, OMIM:618286

Publications

39567597

Created: 4 Feb 2025, 5:01 p.m.
Last Modified: 4 Feb 2025, 5:04 p.m.
Panel version: 8.67

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team: After discussion with the Genomics England Clinical team, it was decided to give NFIB an amber gene rating. Although ID was reported the severity is mild-moderate and on this basis, not considered appropriate for green status on the ID panel. NFIB is associated with a phenotype in OMIM and is probably associated with a phenotype on Gene2Phenotypes. The "Autism Spectrum Disorder" and "watchlist" tags have also been added.
Created: 18 Mar 2019, 11:25 a.m.

Created: 18 Mar 2019, 11:25 a.m.

Panel version: 2.786

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Schanze et al. (PMID: 30388402) report on the phenotype related to NFIB haploinsufficiency.

10 individuals with intragenic NFIB or larger deletions encompassing also other genes as well as 8 individuals with nucleotide variants (5 loss-of-function and 3 missense ones) are described.

Intellectual disability was a universal feature while macrocephaly was noted in the majority of the patients. The phenotype of individuals deletions was similar to the phenotype of intragenic mutations as also seems to be the case with the degree of ID.

Functional studies support loss of function for the pathogenic missense variants reported. Cortical-specific knockout of Nfib in mice results in enlargement of the cortex.

While most of the variants occurred as de novo events, a few individuals had inherited a variant (deletion or nucleotide variant) from a similarly affected parent.

As a result, this gene can be considered for inclusion in the ID panel as green.
Sources: Expert Review, Literature
Created: 12 Nov 2018, 4:15 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Intellectual disability; Macrocephaly

Publications

30388402

Created: 12 Nov 2018, 4:15 p.m.

Panel version: 2.531

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber

Phenotypes

Macrocephaly, acquired, with impaired intellectual development, OMIM:618286

Tags

watchlist Autism Spectrum Disorder

OMIM

600728

Clinvar variants

Variants in NFIB

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

4 Feb 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

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

4 Feb 2025, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: NFIB were set to 30388402; 39567597

4 Feb 2025, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: NFIB were changed from Global developmental delay; Intellectual disability; Macrocephaly; Macrocephaly, acquired, with impaired intellectual development, 618286 to Macrocephaly, acquired, with impaired intellectual development, OMIM:618286

4 Feb 2025, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: NFIB were set to 30388402

4 Feb 2025, Gel status: 2

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: NFIB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

18 Mar 2019, Gel status: 2