BRF1

BRF1 RNA polymerase III transcription initiation factor subunit, the group of General transcription factor IIIB complex subunits |General transcription factors

Basic information

Region (hg38): 14:105209285-105315589

Previous symbols: [ "TAF3B2", "TAF3C", "GTF3B" ]

Links

ENSG00000185024 ∙ NCBI:2972 ∙ OMIM:604902 ∙ HGNC:11551 ∙ Uniprot:Q92994 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar-facial-dental syndrome (Moderate), mode of inheritance: AR
• cerebellar-facial-dental syndrome (Strong), mode of inheritance: AR
• cerebellar-facial-dental syndrome (Strong), mode of inheritance: AR
• cerebellar-facial-dental syndrome (Supportive), mode of inheritance: AR
• colorectal adenoma (Limited), mode of inheritance: AD
• cerebellar-facial-dental syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellofaciodental syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic	25561519

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRF1 gene.

• Inborn genetic diseases (66 variants)
• not provided (64 variants)
• Cerebellar-facial-dental syndrome (11 variants)
• not specified (2 variants)
• BRF1-related condition (2 variants)
• See cases (2 variants)
• 6 conditions (1 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRF1 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				31	5	36
missense	1	3	41	12		57
nonsense						0
start loss						0
frameshift	2	2				4
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)						0
splice region				4		4
non coding			25	4	3	32
Total	3	5	68	48	8

Highest pathogenic variant AF is 0.0000131

Variants in BRF1

This is a list of pathogenic ClinVar variants found in the BRF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-105209632-C-T			Likely benign (Aug 01, 2022)
14-105209633-G-A			Likely benign (Sep 01, 2021)
14-105210578-A-G			Likely benign (Mar 05, 2018)
14-105210580-A-G		Inborn genetic diseases	Uncertain significance (May 17, 2023)
14-105211115-C-T			Likely benign (Jun 16, 2018)
14-105211138-C-T			Likely benign (May 08, 2018)
14-105211164-C-T		Colorectal cancer	Likely pathogenic (Jul 19, 2021)
14-105211165-GTCC-G		Cerebellar-facial-dental syndrome	Uncertain significance (Nov 20, 2023)
14-105211171-C-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
14-105211174-G-A			Likely benign (Jun 26, 2018)
14-105211177-A-G		BRF1-related disorder	Likely benign (Jul 26, 2021)
14-105211184-T-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
14-105211189-G-A			Likely benign (Apr 01, 2023)
14-105211201-G-A		BRF1-related disorder	Likely benign (Sep 05, 2019)
14-105211201-G-C		Inborn genetic diseases	Likely benign (Jun 18, 2021)
14-105211209-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
14-105211219-G-A			Likely benign (Jan 01, 2024)
14-105211228-C-T			Likely benign (Feb 01, 2024)
14-105211241-G-A		Inborn genetic diseases	Likely benign (Oct 03, 2022)
14-105211242-C-T		Inborn genetic diseases	Likely benign (Dec 14, 2021)
14-105211286-A-T			Uncertain significance (Feb 07, 2020)
14-105211292-G-C		Inborn genetic diseases	Likely benign (Jan 23, 2024)
14-105212144-G-A			Uncertain significance (Nov 17, 2022)
14-105217208-A-C			Benign (Mar 01, 2023)
14-105217556-C-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRF1	protein_coding	protein_coding	ENST00000546474	18	106304

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000104	1.00	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.139	421	429	0.981	0.0000280	4406
Missense in Polyphen		104	124.06	0.83829		1242
Synonymous	-3.94	264	194	1.36	0.0000146	1349
Loss of Function	3.38	13	34.4	0.378	0.00000165	405

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000940	0.0000924
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter.
• Disease: DISEASE: Cerebellofaciodental syndrome (CFDS) [MIM:616202]: An autosomal recessive disorder characterized by cerebellar hypoplasia, delayed development and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. {ECO:0000269|PubMed:25561519}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gene expression (Transcription);rna polymerase iii transcription;RNA Polymerase III Abortive And Retractive Initiation;RNA Polymerase III Transcription Initiation From Type 1 Promoter;RNA Polymerase III Transcription Initiation From Type 2 Promoter;RNA Polymerase III Transcription Initiation;RNA Polymerase III Transcription (Consensus)

Intolerance Scores

• loftool: 0.0422
• rvis_EVS: -2.06
• rvis_percentile_EVS: 1.62

Haploinsufficiency Scores

• pHI: 0.310
• hipred: Y
• hipred_score: 0.756
• ghis: 0.700

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brf1

Zebrafish Information Network

• Gene name: brf1a
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: DNA-templated transcription, initiation;transcription by RNA polymerase III;transcription initiation from RNA polymerase III promoter;rRNA transcription;tRNA transcription;positive regulation of transcription by RNA polymerase III;transcription preinitiation complex assembly;RNA polymerase III preinitiation complex assembly
• Cellular component: transcription factor TFIIIB complex;nucleus;nucleoplasm
• Molecular function: RNA polymerase III general transcription initiation factor activity;RNA polymerase III type 3 promoter sequence-specific DNA binding;transcription factor binding;TBP-class protein binding;metal ion binding