BEST1

bestrophin 1, the group of Bestrophins

Basic information

Region (hg38): 11:61950062-61965515

Previous symbols: [ "VMD2" ]

Links

ENSG00000167995 ∙ NCBI:7439 ∙ OMIM:607854 ∙ HGNC:12703 ∙ Uniprot:O76090 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant vitreoretinochoroidopathy (Strong), mode of inheritance: AD
• vitelliform macular dystrophy 2 (Definitive), mode of inheritance: AD
• autosomal dominant vitreoretinochoroidopathy (Moderate), mode of inheritance: AD
• autosomal recessive bestrophinopathy (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• autosomal dominant vitreoretinochoroidopathy (Supportive), mode of inheritance: AD
• vitelliform macular dystrophy 2 (Supportive), mode of inheritance: AD
• nanophthalmia (Supportive), mode of inheritance: AD
• adult-onset foveomacular vitelliform dystrophy (Supportive), mode of inheritance: AD
• autosomal recessive bestrophinopathy (Supportive), mode of inheritance: AR
• MRCS syndrome (Supportive), mode of inheritance: AD
• autosomal recessive bestrophinopathy (Definitive), mode of inheritance: AR
• vitelliform macular dystrophy 2 (Definitive), mode of inheritance: AD
• autosomal recessive bestrophinopathy (Strong), mode of inheritance: AR
• vitelliform macular dystrophy 2 (Strong), mode of inheritance: AD
• autosomal dominant vitreoretinochoroidopathy (Strong), mode of inheritance: AD
• retinitis pigmentosa 50 (Strong), mode of inheritance: AD
• inherited retinal dystrophy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vitreoretinochoroidopathy	AD	Ophthalmologic; Pharmacogenomic	Findings such as glaucoma and retinal detachment have been described, and surveillance and early treatment (eg, direct laser photocoagulation and anti-vascular endothelial growth factors for choroidal neovascularization and hemorrhage), as well as preventive measures, may be beneficial; Agents that may contribute to glaucoma, as well as smoking, should be avoided	Ophthalmologic	13546939; 838599; 7065944; 6689931; 8431155; 9662395; 10453731; 10331951; 10854112; 10737974; 11585313; 12543751; 15452077; 16458719; 16678511; 17698758; 17591911; 18179881; 18611979; 19853238; 20057903; 20301346; 20375334; 20847757; 21192766; 21320969; 22422030; 22584882; 22633354; 23290749; 23572118; 23765342; 23823511; 24345323

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BEST1 gene.

• not provided (706 variants)
• Vitelliform macular dystrophy 2 (123 variants)
• Autosomal dominant vitreoretinochoroidopathy (62 variants)
• Retinitis pigmentosa (53 variants)
• Retinal dystrophy (45 variants)
• Autosomal recessive bestrophinopathy (31 variants)
• Retinitis Pigmentosa, Recessive (20 variants)
• Iron Overload (17 variants)
• not specified (16 variants)
• Hemochromatosis type 5 (13 variants)
• Retinitis pigmentosa 50 (10 variants)
• Inborn genetic diseases (10 variants)
• BEST1-related condition (10 variants)
• Autosomal recessive bestrophinopathy;Vitelliform macular dystrophy 2;Autosomal dominant vitreoretinochoroidopathy;Retinitis pigmentosa 50 (4 variants)
• Stargardt disease (4 variants)
• Macular dystrophy (3 variants)
• Autosomal recessive bestrophinopathy;Autosomal dominant vitreoretinochoroidopathy;Vitelliform macular dystrophy 2;Retinitis pigmentosa 50 (2 variants)
• Isolated macular dystrophy (2 variants)
• Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 2 (1 variants)
• See cases (1 variants)
• Rod-cone dystrophy (1 variants)
• Cone-rod dystrophy 6 (1 variants)
• BEST1-Related Disorders (1 variants)
• Vitelliform macular dystrophy 1 (1 variants)
• FTH1-related condition (1 variants)
• Autosomal dominant vitreoretinochoroidopathy;Vitelliform macular dystrophy 2;Retinitis pigmentosa 50;Autosomal recessive bestrophinopathy (1 variants)
• Autosomal recessive bestrophinopathy;Autosomal dominant vitreoretinochoroidopathy;Retinitis pigmentosa 50;Vitelliform macular dystrophy 2 (1 variants)
• maculopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BEST1 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	1		2	91	8	102
missense	89	93	203	5	3	393
nonsense	12	7	2			21
start loss	1					1
frameshift	17	3				20
inframe indel		3	8			11
splice donor/acceptor (+/-2bp)	3	8			1	12
splice region		1	10	14		25
non coding			23	49	41	113
Total	123	114	238	145	53

Highest pathogenic variant AF is 0.0000329

Variants in BEST1

This is a list of pathogenic ClinVar variants found in the BEST1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-61950091-T-A		Vitelliform macular dystrophy 2 • Retinitis Pigmentosa, Recessive • Autosomal dominant vitreoretinochoroidopathy	Likely benign (Jun 14, 2016)
11-61950135-C-T		Vitelliform macular dystrophy 2 • Autosomal dominant vitreoretinochoroidopathy • Retinitis Pigmentosa, Recessive	Benign (Jul 07, 2018)
11-61950243-T-C		Vitelliform macular dystrophy 2 • Retinitis Pigmentosa, Recessive • Autosomal dominant vitreoretinochoroidopathy	Benign (Jun 26, 2018)
11-61950339-G-A		Autosomal dominant vitreoretinochoroidopathy • Vitelliform macular dystrophy 2 • Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
11-61950343-C-T		Autosomal dominant vitreoretinochoroidopathy • Vitelliform macular dystrophy 2 • Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
11-61950398-G-T		Vitelliform macular dystrophy 2 • Autosomal dominant vitreoretinochoroidopathy • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
11-61950428-G-T		Retinal dystrophy • Autosomal recessive bestrophinopathy	Likely pathogenic (Jan 30, 2021)
11-61950432-G-A			Likely pathogenic (Jun 26, 2023)
11-61950564-G-A			Benign (Jun 26, 2018)
11-61950701-G-A			Likely benign (Jul 09, 2018)
11-61950756-T-C			Likely benign (Jul 14, 2018)
11-61951554-G-A			Benign (Jul 09, 2018)
11-61951598-T-C			Benign (Jul 10, 2018)
11-61951807-A-G			Pathogenic (May 29, 2022)
11-61951811-C-G		Retinal dystrophy	Pathogenic/Likely pathogenic (Oct 12, 2021)
11-61951814-T-A			Likely pathogenic (Feb 07, 2023)
11-61951817-C-T			Pathogenic (Aug 12, 2022)
11-61951819-T-A			Uncertain significance (Aug 24, 2023)
11-61951822-A-C		Vitelliform macular dystrophy 2	Pathogenic (Aug 01, 2007)
11-61951822-A-G		Retinal dystrophy	Pathogenic/Likely pathogenic (Nov 27, 2023)
11-61951823-C-A		Vitelliform macular dystrophy 2	Likely pathogenic (Dec 20, 2022)
11-61951823-C-G			Pathogenic/Likely pathogenic (Nov 10, 2023)
11-61951826-G-A			Uncertain significance (May 15, 2023)
11-61951831-G-A		Vitelliform macular dystrophy 2	Pathogenic (Sep 01, 1998)
11-61951831-G-C			Pathogenic (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BEST1	protein_coding	protein_coding	ENST00000449131	8	15695

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.82e-12	0.0314	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.617	289	320	0.903	0.0000178	3952
Missense in Polyphen		74	103.35	0.71605		1255
Synonymous	0.804	122	134	0.912	0.00000794	1181
Loss of Function	-0.0233	18	17.9	1.01	8.53e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000381	0.000381
South Asian	0.0000344	0.0000327
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms calcium-sensitive chloride channels. Highly permeable to bicarbonate. {ECO:0000269|PubMed:11904445, ECO:0000269|PubMed:12907679, ECO:0000269|PubMed:18400985}.
• Disease: DISEASE: Macular dystrophy, vitelliform, 2 (VMD2) [MIM:153700]: An autosomal dominant form of macular degeneration that usually begins in childhood or adolescence. VMD2 is characterized by typical 'egg-yolk' macular lesions due to abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. Progression of the disease leads to destruction of the retinal pigment epithelium and vision loss. {ECO:0000269|PubMed:10331951, ECO:0000269|PubMed:10394929, ECO:0000269|PubMed:10453731, ECO:0000269|PubMed:10682987, ECO:0000269|PubMed:10798642, ECO:0000269|PubMed:11241846, ECO:0000269|PubMed:11449320, ECO:0000269|PubMed:12187431, ECO:0000269|PubMed:12324875, ECO:0000269|PubMed:13129869, ECO:0000269|PubMed:14517959, ECO:0000269|PubMed:15176385, ECO:0000269|PubMed:18400985, ECO:0000269|PubMed:18766995, ECO:0000269|PubMed:19357557, ECO:0000269|PubMed:21330666, ECO:0000269|PubMed:9662395, ECO:0000269|PubMed:9700209}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 50 (RP50) [MIM:613194]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:19853238}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bestrophinopathy, autosomal recessive (ARB) [MIM:611809]: A retinopathy characterized by loss of central vision, an absent electro-oculogram light rise, and electroretinogram anomalies. {ECO:0000269|PubMed:18179881, ECO:0000269|PubMed:19853238, ECO:0000269|PubMed:21330666, ECO:0000269|PubMed:26200502, ECO:0000269|PubMed:26720466}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Vitreoretinochoroidopathy, autosomal dominant (ADVIRC) [MIM:193220]: A disorder characterized by vitreoretinochoroidal dystrophy. The clinical presentation is variable. VRCP may be associated with cataract, nanophthalmos, microcornea, shallow anterior chamber, and glaucoma. {ECO:0000269|PubMed:15452077}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.0103
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.66

Haploinsufficiency Scores

• pHI: 0.134
• hipred: N
• hipred_score: 0.180
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.827

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Best1
• Phenotype: cellular phenotype; pigmentation phenotype; reproductive system phenotype; vision/eye phenotype

Gene ontology

• Biological process: chloride transport;visual perception;bicarbonate transport;transepithelial chloride transport;ion transmembrane transport;detection of light stimulus involved in visual perception;regulation of calcium ion transport;chloride transmembrane transport
• Cellular component: cytosol;plasma membrane;membrane;integral component of membrane;basolateral plasma membrane;chloride channel complex
• Molecular function: intracellular calcium activated chloride channel activity;chloride channel activity;bicarbonate transmembrane transporter activity;identical protein binding