11-61951915-T-C

Position:

chr11-61951915-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004183.4(BEST1):c.109T>C(p.Leu37Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,370 control chromosomes in the GnomAD database, including 145,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21404 hom., cov: 32)

Exomes 𝑓: 0.38 ( 123599 hom. )

Consequence

BEST1
NM_004183.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17O:1

Conservation

PhyloP100: -0.761

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:

BEST1 (HGNC:):

BEST1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 11-61951915-T-C is Benign according to our data. Variant chr11-61951915-T-C is described in ClinVar as [Benign]. Clinvar id is 99678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61951915-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.761 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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.109T>C	p.Leu37Leu	synonymous_variant	2/11	ENST00000378043.9	NP_004174.1	O76090-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000378043.9 linkuse as main transcript	c.109T>C	p.Leu37Leu	synonymous_variant	2/11	1	NM_004183.4	ENSP00000367282.4		O76090-1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74763

AN:

152006

Hom.:

21364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.488

AC:

122451

AN:

251064

Hom.:

35490

AF XY:

0.480

AC XY:

65222

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.912

Gnomad SAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.380

AC:

555789

AN:

1461246

Hom.:

123599

Cov.:

AF XY:

0.387

AC XY:

281424

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.609

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.934

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.492

AC:

74857

AN:

152124

Hom.:

21404

Cov.:

AF XY:

0.504

AC XY:

37507

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.732

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.348

Hom.:

22758

Bravo

AF:

0.503

Asia WGS

AF:

0.768

AC:

2668

AN:

3478

EpiCase

AF:

0.304

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:17Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 28, 2017	- -
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	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:4Other:1

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

Autosomal dominant vitreoretinochoroidopathy

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Vitelliform macular dystrophy 2

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Autosomal recessive bestrophinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Retinitis pigmentosa 50

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

-0.42

CADD

Benign

5.9

DANN

Benign

0.60

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