Variant chr11-61950135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363592.1(BEST1):c.-329C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,354 control chromosomes in the GnomAD database, including 3,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3473 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3 hom. )

Consequence

BEST1
NM_001363592.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.194

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 11-61950135-C-T is Benign according to our data. Variant chr11-61950135-C-T is described in ClinVar as [Benign]. Clinvar id is 305112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
BEST1	NM_001363592.1 linkuse as main transcript	c.-329C>T	5_prime_UTR_variant	1/10
BEST1	XM_005274210.5 linkuse as main transcript	c.-329C>T	5_prime_UTR_variant	1/10
BEST1	XM_005274221.5 linkuse as main transcript	c.-329C>T	5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEST1	ENST00000534553.5 linkuse as main transcript	c.-504C>T		5_prime_UTR_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25535

AN:

152016

Hom.:

3466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.132

AC:

AN:

220

Hom.:

Cov.:

AF XY:

0.151

AC XY:

AN XY:

146

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0909

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.168

AC:

25564

AN:

152134

Hom.:

3473

Cov.:

AF XY:

0.179

AC XY:

13297

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.0643

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.121

Hom.:

335

Bravo

AF:

0.174

Asia WGS

AF:

0.550

AC:

1906

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.89

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