NM_004183.4(BEST1):c.886A>C (p.Asn296His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 16, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000086181.6

Allele description [Variation Report for NM_004183.4(BEST1):c.886A>C (p.Asn296His)]

NM_004183.4(BEST1):c.886A>C (p.Asn296His)

Gene:

BEST1:bestrophin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.3

Genomic location:

Preferred name:

NM_004183.4(BEST1):c.886A>C (p.Asn296His)

HGVS:

NC_000011.10:g.61959516A>C
NG_009033.1:g.14633A>C
NM_001139443.2:c.706A>C
NM_001300786.2:c.688-376A>C
NM_001300787.2:c.706A>C
NM_001363591.2:c.568A>C
NM_001363592.1:c.1089A>C
NM_001363593.2:c.-87A>C
NM_004183.4:c.886A>CMANE SELECT
NP_001132915.1:p.Asn236His
NP_001287716.1:p.Asn236His
NP_001350520.1:p.Asn190His
NP_001350521.1:p.Ser363=
NP_004174.1:p.Asn296His
NC_000011.9:g.61726988A>C
NM_004183.3:c.886A>C
NR_134580.2:n.1202A>C
O76090:p.Asn296His

Protein change:

N190H

Links:

UniProtKB: O76090#VAR_025744; dbSNP: rs281865254

NCBI 1000 Genomes Browser:

rs281865254

Molecular consequence:

NM_001363593.2:c.-87A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300786.2:c.688-376A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001139443.2:c.706A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.706A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.568A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.886A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.1202A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001363592.1:c.1089A>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118325	Retina International	no classification provided	not provided	not provided	not provided
SCV001574116	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10798642, 17110374, 11241846, 17296903, 17698758, 27031371, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118325

Retina International

no classification provided

not provided

SCV001574116

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 16, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_VMD2:c.886A>C: SCV000118325

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.

Lotery AJ, Munier FL, Fishman GA, Weleber RG, Jacobson SG, Affatigato LM, Nichols BE, Schorderet DF, Sheffield VC, Stone EM.

Invest Ophthalmol Vis Sci. 2000 May;41(6):1291-6.

PubMed [citation]

PMID:: 10798642

Insertion and topology of normal and mutant bestrophin-1 in the endoplasmic reticulum membrane.

Milenkovic VM, Rivera A, Horling F, Weber BH.

J Biol Chem. 2007 Jan 12;282(2):1313-21. Epub 2006 Nov 15.

PubMed [citation]

PMID:: 17110374

See all PubMed Citations (7)

Details of each submission

From Retina International, SCV000118325.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001574116.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 296 of the BEST1 protein (p.Asn296His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant BEST1-related conditions (PMID: 10798642; Invitae). ClinVar contains an entry for this variant (Variation ID: 99763). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BEST1 protein function. Experimental studies have shown that this missense change does not substantially affect BEST1 function (PMID: 17110374). This variant disrupts the p.Asn296 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 11241846, 17296903, 17698758, 27031371), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine