chr11-61962762-T-C

Position:

chr11-61962762-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004183.4(BEST1):c.1608T>C(p.Thr536=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,872 control chromosomes in the GnomAD database, including 138,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15332 hom., cov: 32)

Exomes 𝑓: 0.39 ( 122866 hom. )

Consequence

BEST1
NM_004183.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15O:1

Conservation

PhyloP100: -1.12

Variant links:

Genes affected

BEST1 (HGNC:12703): (bestrophin 1) This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Nov 2008]

BEST1 links:

FTH1 (HGNC:3976): (ferritin heavy chain 1) This gene encodes the heavy subunit of ferritin, the major intracellular iron storage protein in prokaryotes and eukaryotes. It is composed of 24 subunits of the heavy and light ferritin chains. Variation in ferritin subunit composition may affect the rates of iron uptake and release in different tissues. A major function of ferritin is the storage of iron in a soluble and nontoxic state. Defects in ferritin proteins are associated with several neurodegenerative diseases. This gene has multiple pseudogenes. Several alternatively spliced transcript variants have been observed, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

FTH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-61962762-T-C is Benign according to our data. Variant chr11-61962762-T-C is described in ClinVar as [Benign]. Clinvar id is 99682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61962762-T-C is described in Lovd as [Benign]. Variant chr11-61962762-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST1	NM_004183.4 linkuse as main transcript	c.1608T>C	p.Thr536=	synonymous_variant	10/11	ENST00000378043.9	NP_004174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000378043.9 linkuse as main transcript	c.1608T>C	p.Thr536=	synonymous_variant	10/11	1	NM_004183.4	ENSP00000367282	P1	O76090-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65727

AN:

151896

Hom.:

15321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.410

GnomAD3 exomes

AF:

0.460

AC:

115612

AN:

251412

Hom.:

29871

AF XY:

0.462

AC XY:

62801

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.861

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.391

AC:

570908

AN:

1461858

Hom.:

122866

Cov.:

AF XY:

0.398

AC XY:

289639

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.904

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.433

AC:

65788

AN:

152014

Hom.:

15332

Cov.:

AF XY:

0.444

AC XY:

32975

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.864

Gnomad4 SAS

AF:

0.699

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.409

Alfa

AF:

0.374

Hom.:

6309

Bravo

AF:

0.438

Asia WGS

AF:

0.712

AC:

2478

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.350

ClinVar

Significance: Benign

Submissions summary: Benign:15Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 16, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:4Other:1

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Retinitis Pigmentosa, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant vitreoretinochoroidopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Vitelliform macular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Iron Overload

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.53

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over