FANCB

FA complementation group B, the group of FA complementation groups|FA core complex

Basic information

Region (hg38): X:14690387-14873255

Links

ENSG00000181544 ∙ NCBI:2187 ∙ OMIM:300515 ∙ HGNC:3583 ∙ Uniprot:Q8NB91 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• VACTERL association, X-linked, with or without hydrocephalus (Strong), mode of inheritance: XL
• Fanconi anemia complementation group B (Strong), mode of inheritance: XL
• Fanconi anemia complementation group B (Definitive), mode of inheritance: XLR
• Fanconi anemia (Supportive), mode of inheritance: AR
• VACTERL with hydrocephalus (Supportive), mode of inheritance: AR
• Fanconi anemia complementation group B (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia,complementation group B	XL	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	15502827; 16679491; 20301575; 21910217; 22052692

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FANCB gene.

• Fanconi anemia (409 variants)
• not provided (62 variants)
• Fanconi anemia complementation group B (59 variants)
• VACTERL association, X-linked, with or without hydrocephalus (42 variants)
• not specified (34 variants)
• Inborn genetic diseases (30 variants)
• VACTERL association, X-linked, with or without hydrocephalus;Fanconi anemia complementation group B (15 variants)
• Fanconi anemia complementation group B;VACTERL association, X-linked, with or without hydrocephalus (13 variants)
• FANCB-related condition (8 variants)
• X-linked central congenital hypothyroidism with late-onset testicular enlargement (6 variants)
• VACTERL with hydrocephalus (3 variants)
• Fanconi Anemia, X-Linked (3 variants)
• History of neurodevelopmental disorder (3 variants)
• Intellectual developmental disorder, X-linked, syndromic, Pilorge type (2 variants)
• Fanconi anemia complementation group A (1 variants)
• See cases (1 variants)
• GLRA2-related condition (1 variants)
• Malignant tumor of breast (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	104	15	122
missense		1	204	36	5	246
nonsense	2		2			4
start loss						0
frameshift	4	2				6
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2	1			3
splice region			6	9	5	20
non coding		1	10	27	21	59
Total	6	6	222	167	41

Highest pathogenic variant AF is 0.0000451

Variants in FANCB

This is a list of pathogenic ClinVar variants found in the FANCB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-14690691-G-C			Benign (Feb 03, 2022)
X-14690691-GTC-G		Inborn genetic diseases	Benign (Mar 17, 2022)
X-14690691-G-GTCTC		GLRA2-related disorder	Likely benign (May 26, 2020)
X-14690827-C-T		Intellectual developmental disorder, X-linked, syndromic, Pilorge type • Inborn genetic diseases	Uncertain significance (Jul 01, 2023)
X-14690828-G-T		Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Pathogenic (Aug 01, 2011)
X-14690853-G-A		GLRA2-related disorder	Likely benign (Jan 10, 2023)
X-14730202-G-A		Inborn genetic diseases	Likely benign (Sep 01, 2021)
X-14730215-C-T		GLRA2-related disorder	Benign (Dec 31, 2019)
X-14730225-G-C			Uncertain significance (Nov 05, 2023)
X-14730254-G-A		GLRA2-related disorder	Likely benign (Feb 20, 2019)
X-14730288-G-C		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
X-14730298-C-T		GLRA2-related disorder	Likely benign (Jun 06, 2023)
X-14730312-C-A		See cases • Intellectual developmental disorder, X-linked, syndromic, Pilorge type	Likely pathogenic (Nov 29, 2022)
X-14730325-C-T		See cases	Likely pathogenic (Jan 10, 2022)
X-14730347-C-G		GLRA2-related disorder	Uncertain significance (Jan 10, 2023)
X-14730385-C-T		Inborn genetic diseases	Uncertain significance (Dec 14, 2022)
X-14730460-G-A		See cases	Likely pathogenic (Jan 10, 2022)
X-14730476-C-G			Uncertain significance (Nov 01, 2022)
X-14796834-A-G			Likely benign (Mar 01, 2024)
X-14796872-C-T			Uncertain significance (Mar 01, 2023)
X-14796910-G-A			Likely benign (Mar 01, 2024)
X-14843282-T-C			Benign (Jan 10, 2019)
X-14843416-T-C		Fanconi anemia complementation group B • VACTERL association, X-linked, with or without hydrocephalus	Uncertain significance (Jan 12, 2018)
X-14843501-A-C		Fanconi anemia complementation group B • VACTERL association, X-linked, with or without hydrocephalus	Benign (Jan 12, 2018)
X-14843534-A-G		VACTERL association, X-linked, with or without hydrocephalus • Fanconi anemia complementation group B	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCB	protein_coding	protein_coding	ENST00000398334	8	29663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00369	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0417	294	292	1.01	0.0000205	5676
Missense in Polyphen		44	62.452	0.70455		1433
Synonymous	0.427	101	107	0.947	0.00000767	1596
Loss of Function	4.04	1	20.9	0.0478	0.00000137	475

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA repair protein required for FANCD2 ubiquitination. {ECO:0000269|PubMed:15502827}.
• Disease: DISEASE: Fanconi anemia complementation group B (FANCB) [MIM:300514]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some severe FANCB cases manifest features of VACTERL syndrome with hydrocephalus. {ECO:0000269|PubMed:16679491}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;Fanconi anemia pathway (Consensus)

Recessive Scores

• pRec: 0.317

Intolerance Scores

• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.110
• hipred: Y
• hipred_score: 0.667
• ghis: 0.421

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fancb
• Phenotype: reproductive system phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: interstrand cross-link repair;positive regulation of double-strand break repair via homologous recombination;replication-born double-strand break repair via sister chromatid exchange;negative regulation of double-strand break repair via homologous recombination
• Cellular component: nucleoplasm;Fanconi anaemia nuclear complex
• Molecular function: protein binding