BRIP1

BRCA1 interacting helicase 1, the group of BRCA1 B complex|DNA helicases|FA complementation groups

Basic information

Region (hg38): 17:61679139-61863559

Links

ENSG00000136492 ∙ NCBI:83990 ∙ OMIM:605882 ∙ HGNC:20473 ∙ Uniprot:Q9BX63 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia (Supportive), mode of inheritance: AR
• colorectal adenoma (Limited), mode of inheritance: AD
• Fanconi anemia (Definitive), mode of inheritance: AR
• hereditary breast carcinoma (Strong), mode of inheritance: AD
• Fanconi anemia complementation group J (Strong), mode of inheritance: AR
• Fanconi anemia complementation group J (Definitive), mode of inheritance: AR
• hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD
• familial ovarian cancer (Definitive), mode of inheritance: AD
• Fanconi anemia complementation group J (Definitive), mode of inheritance: AR
• hereditary breast carcinoma (Strong), mode of inheritance: AD
• Fanconi anemia complementation group J (Strong), mode of inheritance: AR
• hereditary breast carcinoma (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	AD/AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	For Breast cancer, awareness may allow early surveillance, preventive measures, and early diagnosis and treatment of disease; For Fanconi anemia, 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; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	11301010; 14630800; 14983014; 16116424; 16116423; 17033622; 21568838; 21964575; 22006311; 22441895; 23285130
Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRIP1 gene.

• Familial_cancer_of_breast (4620 variants)
• Fanconi_anemia_complementation_group_J (4119 variants)
• Hereditary_cancer-predisposing_syndrome (3772 variants)
• not_provided (973 variants)
• not_specified (545 variants)
• Ovarian_cancer (200 variants)
• Familial_ovarian_cancer (145 variants)
• BRIP1-related_disorder (137 variants)
• Hereditary_breast_ovarian_cancer_syndrome (123 variants)
• Breast_and/or_ovarian_cancer (87 variants)
• Malignant_tumor_of_breast (59 variants)
• Gastric_cancer (26 variants)
• Breast-ovarian_cancer,_familial,_susceptibility_to,_1 (9 variants)
• Hereditary_cancer (9 variants)
• Breast_carcinoma (8 variants)
• Ovarian_neoplasm (7 variants)
• Inherited_ovarian_cancer_(without_breast_cancer) (6 variants)
• Breast_cancer,_early-onset (6 variants)
• Fanconi_anemia (5 variants)
• BRIP1-associated_familial_cancer_predisposition (4 variants)
• Breast_neoplasm (4 variants)
• Breast-ovarian_cancer,_familial,_susceptibility_to,_2 (2 variants)
• Carcinoma_of_colon (2 variants)
• Carcinoma_of_pancreas (2 variants)
• Uterine_corpus_cancer (1 variants)
• Esophageal_atresia/tracheoesophageal_fistula (1 variants)
• Cervical_cancer (1 variants)
• Hereditary_skin_disorder (1 variants)
• Fanconi_anemia_complementation_group_D2 (1 variants)
• Neurodevelopmental_delay (1 variants)
• Diffuse_intrinsic_pontine_glioma (1 variants)
• Genetic_non-acquired_premature_ovarian_failure (1 variants)
• Colorectal_cancer (1 variants)
• Ovarian_cancer,_susceptibility_to,_1 (1 variants)
• Ovarian_Cancers (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRIP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032043.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2	3	18	1034	108	1165
missense	20	23	2786	170	6	3005
nonsense	153	66	17			236
start loss	2	2	3			7
frameshift	398	139	74			611
splice donor/acceptor (+/-2bp)	4	139	11	1		155
Total	579	372	2909	1205	114

Highest pathogenic variant AF is 0.000286946

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRIP1	protein_coding	protein_coding	ENST00000259008	19	182256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.21e-17	0.996	125549	0	199	125748	0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	553	638	0.866	0.0000322	8208
Missense in Polyphen		174	229.1	0.7595		2855
Synonymous	0.647	211	223	0.945	0.0000110	2329
Loss of Function	2.92	36	60.5	0.595	0.00000313	790

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00151	0.00151
Ashkenazi Jewish	0.00	0.00
East Asian	0.00109	0.00109
Finnish	0.000821	0.000786
European (Non-Finnish)	0.000974	0.000967
Middle Eastern	0.00109	0.00109
South Asian	0.000427	0.000425
Other	0.000824	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1. {ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:14983014, ECO:0000269|PubMed:16116421, ECO:0000269|PubMed:16153896}.
• Disease: DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:14983014}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Fanconi anemia complementation group J (FANCJ) [MIM:609054]: 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:16116423, ECO:0000269|PubMed:16116424, ECO:0000269|PubMed:20639400}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Processing of DNA double-strand break ends;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.271

Intolerance Scores

• loftool: 0.640
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.74

Haploinsufficiency Scores

• pHI: 0.208
• hipred: Y
• hipred_score: 0.599
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.817

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brip1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); liver/biliary system phenotype; reproductive system phenotype; endocrine/exocrine gland phenotype; neoplasm; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA damage checkpoint;DNA replication;nucleotide-excision repair;double-strand break repair;regulation of transcription by RNA polymerase II;spermatogonial cell division;spermatid development;negative regulation of cell population proliferation;response to toxic substance;negative regulation of gene expression;meiotic DNA double-strand break processing involved in reciprocal meiotic recombination;DNA duplex unwinding;chiasma assembly;cellular response to vitamin;cellular response to hypoxia;seminiferous tubule development;cellular response to angiotensin;double-strand break repair involved in meiotic recombination
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear membrane
• Molecular function: DNA binding;chromatin binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;metal ion binding;4 iron, 4 sulfur cluster binding