FANCI

FA complementation group I, the group of FA complementation groups

Basic information

Region (hg38): 15:89243945-89317261

Previous symbols: [ "KIAA1794" ]

Links

ENSG00000140525 ∙ NCBI:55215 ∙ OMIM:611360 ∙ HGNC:25568 ∙ Uniprot:Q9NVI1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia complementation group I (Strong), mode of inheritance: AR
• Fanconi anemia complementation group I (Definitive), mode of inheritance: AR
• Fanconi anemia (Supportive), mode of inheritance: AR
• Fanconi anemia complementation group I (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group I	AR	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	14630800; 17452773; 17460694; 17412408; 20301575; 21568838

ClinVar

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

• Fanconi anemia (66 variants)
• Fanconi anemia complementation group I (6 variants)
• not provided (2 variants)
• Progressive sclerosing poliodystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCI 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			6	370	5	381
missense		2	667	13	8	690
nonsense	30	34				64
start loss			2			2
frameshift	38	59	3			100
inframe indel			14			14
splice donor/acceptor (+/-2bp)		54	2		1	57
splice region		1	50	102	6	159
non coding	1		58	391	93	543
Total	69	149	752	774	107

Highest pathogenic variant AF is 0.000177

Variants in FANCI

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

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

Position	Type	Phenotype	Significance	ClinVar
15-89243963-T-C		Fanconi anemia complementation group I	Uncertain significance (Jan 13, 2018)
15-89243981-C-G		Fanconi anemia complementation group I	Uncertain significance (Jan 13, 2018)
15-89243997-T-C		Fanconi anemia complementation group I	Uncertain significance (Jan 13, 2018)
15-89244030-G-A		Fanconi anemia complementation group I	Uncertain significance (Jan 12, 2018)
15-89247480-A-G			Benign (Jul 09, 2018)
15-89247638-A-G		Fanconi anemia complementation group I	Uncertain significance (Mar 21, 2022)
15-89247646-C-A		FANCI-related disorder	Likely benign (Apr 23, 2021)
15-89247648-A-G		Fanconi anemia • Fanconi anemia complementation group I	Uncertain significance (Sep 16, 2021)
15-89247649-T-C		Fanconi anemia complementation group I	Pathogenic (Feb 07, 2011)
15-89247649-T-G		Fanconi anemia	Uncertain significance (May 25, 2022)
15-89247651-G-T		Fanconi anemia	Uncertain significance (Nov 10, 2020)
15-89247652-A-T			Uncertain significance (Nov 03, 2021)
15-89247655-A-G		Fanconi anemia	Uncertain significance (Mar 11, 2022)
15-89247656-G-C		Fanconi anemia	Uncertain significance (Sep 20, 2023)
15-89247659-G-C		Fanconi anemia	Uncertain significance (Apr 06, 2021)
15-89247660-A-G		Fanconi anemia • Fanconi anemia complementation group I	Uncertain significance (Sep 06, 2022)
15-89247663-T-G		Fanconi anemia	Uncertain significance (Jul 06, 2022)
15-89247664-T-C		Fanconi anemia • Fanconi anemia complementation group I	Uncertain significance (Mar 23, 2022)
15-89247665-A-G		Fanconi anemia	Likely benign (Dec 19, 2019)
15-89247669-C-G		Fanconi anemia	Uncertain significance (Jul 25, 2022)
15-89247671-A-G		Fanconi anemia	Likely benign (Aug 17, 2023)
15-89247672-G-A		Fanconi anemia complementation group I	Uncertain significance (May 31, 2021)
15-89247672-G-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
15-89247679-A-G		Fanconi anemia	Uncertain significance (Dec 26, 2021)
15-89247680-A-G		Fanconi anemia	Likely benign (Mar 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCI	protein_coding	protein_coding	ENST00000310775	37	73313

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.91e-37	0.000982	125498	0	250	125748	0.000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.35	747	650	1.15	0.0000325	8740
Missense in Polyphen		114	118.33	0.96338		1739
Synonymous	-1.78	274	239	1.15	0.0000127	2471
Loss of Function	1.37	63	75.9	0.830	0.00000377	971

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00181	0.00181
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000829	0.000816
Finnish	0.00337	0.00338
European (Non-Finnish)	0.000634	0.000633
Middle Eastern	0.000829	0.000816
South Asian	0.00124	0.00124
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an essential role in the repair of DNA double- strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single- stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage. {ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17452773, ECO:0000269|PubMed:17460694, ECO:0000269|PubMed:19111657}.
• Disease: DISEASE: Fanconi anemia complementation group I (FANCI) [MIM:609053]: 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. {ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17452773, ECO:0000269|PubMed:17460694}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Gastric Cancer Network 2;TP53 Regulates Transcription of DNA Repair Genes;Fanconi Anemia Pathway;DNA Repair;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Fanconi anemia pathway;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.265
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.550
• ghis: 0.661

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Fanci
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: cell cycle;positive regulation of protein ubiquitination;interstrand cross-link repair
• Cellular component: nucleoplasm;cytosol;membrane
• Molecular function: DNA binding;protein binding;DNA polymerase binding