BBS7

Bardet-Biedl syndrome 7, the group of BBSome

Basic information

Region (hg38): 4:121824328-121870487

Links

ENSG00000138686 ∙ NCBI:55212 ∙ OMIM:607590 ∙ HGNC:18758 ∙ Uniprot:Q8IWZ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 7 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 7 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome 7 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 7	AR	Cardiovascular; Endocrine	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management; Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	12567324; 21937992; 20301537; 22410627; 36356613
Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BBS7 gene.

• Bardet-Biedl syndrome (441 variants)
• Bardet-Biedl syndrome 7 (176 variants)
• not provided (52 variants)
• Inborn genetic diseases (29 variants)
• not specified (20 variants)
• BBS7-related condition (19 variants)
• Bardet-Biedl syndrome 1 (7 variants)
• Retinal dystrophy (4 variants)
• Retinitis pigmentosa (2 variants)
• See cases (1 variants)
• Bardet-Biedl syndrome 1/7, digenic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS7 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			4	77	2	83
missense	3	5	208	1		217
nonsense	12	11				23
start loss						0
frameshift	20	20				40
inframe indel	2	1	1			4
splice donor/acceptor (+/-2bp)	2	16	1			19
splice region			15	14	1	30
non coding			24	70	31	125
Total	39	53	238	148	33

Highest pathogenic variant AF is 0.0000592

Variants in BBS7

This is a list of pathogenic ClinVar variants found in the BBS7 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-121824334-G-A		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121824499-T-A		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121824536-C-T		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121824574-C-T		Bardet-Biedl syndrome 7	Benign (Jan 12, 2018)
4-121824648-CAAT-C		Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
4-121824658-C-T		Bardet-Biedl syndrome 7	Benign (Jan 12, 2018)
4-121824699-T-C		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121824721-A-G		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121824864-A-G		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121824928-A-C		Bardet-Biedl syndrome 7	Benign (Jan 12, 2018)
4-121825032-T-C		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121825130-TC-T		Bardet-Biedl syndrome	Benign (Jun 14, 2016)
4-121825136-G-A		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121825151-C-G		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121825170-A-G		Bardet-Biedl syndrome 7	Benign (Jan 13, 2018)
4-121825255-C-T		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121825347-G-A		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121825441-A-T		Bardet-Biedl syndrome 7	Benign (Jan 13, 2018)
4-121825507-C-T		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121825556-T-G		Bardet-Biedl syndrome 7	Uncertain significance (Jan 13, 2018)
4-121825587-A-G		Bardet-Biedl syndrome 7	Uncertain significance (Jan 12, 2018)
4-121825610-A-C		Bardet-Biedl syndrome 7	Benign (Jan 13, 2018)
4-121825862-A-G		Bardet-Biedl syndrome	Uncertain significance (Oct 17, 2022)
4-121825866-T-C		Bardet-Biedl syndrome	Likely benign (Jan 13, 2022)
4-121825871-C-T		Bardet-Biedl syndrome 7	Uncertain significance (May 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS7	protein_coding	protein_coding	ENST00000264499	19	46058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.05e-9	0.999	125607	0	140	125747	0.000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	307	374	0.821	0.0000181	4715
Missense in Polyphen		72	100.08	0.71941		1260
Synonymous	1.55	108	131	0.827	0.00000637	1326
Loss of Function	2.88	20	39.6	0.506	0.00000177	513

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000993	0.000993
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000761	0.000761
Finnish	0.000745	0.000739
European (Non-Finnish)	0.000643	0.000633
Middle Eastern	0.000761	0.000761
South Asian	0.000396	0.000392
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
• Disease: DISEASE: Bardet-Biedl syndrome 7 (BBS7) [MIM:615984]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:12567324, ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:15770229, ECO:0000269|PubMed:21344540}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.179

Intolerance Scores

• loftool: 0.384
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.182
• hipred: Y
• hipred_score: 0.637
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.311

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bbs7
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: bbs7
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: eye development;heart looping;regulation of transcription by RNA polymerase II;smoothened signaling pathway;determination of left/right symmetry;brain development;visual perception;protein localization;protein transport;melanosome transport;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;fat cell differentiation;intracellular transport;digestive tract morphogenesis;pigment granule aggregation in cell center;limb development;cilium assembly;primary palate development;non-motile cilium assembly
• Cellular component: photoreceptor outer segment;nucleus;centrosome;cytosol;axoneme;membrane;BBSome;ciliary basal body;ciliary membrane
• Molecular function: RNA polymerase II repressing transcription factor binding;protein binding