Variant chr11-61950091-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001363592.1(BEST1):c.-373T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 152,588 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 4 hom., cov: 32)

Exomes 𝑓: 0.013 ( 0 hom. )

Consequence

BEST1
NM_001363592.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.967

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-61950091-T-A is Benign according to our data. Variant chr11-61950091-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 305111.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00737 (1122/152278) while in subpopulation NFE AF= 0.0113 (769/68004). AF 95% confidence interval is 0.0106. There are 4 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
BEST1	NM_001363592.1 linkuse as main transcript	c.-373T>A	5_prime_UTR_variant	1/10	NP_001350521.1
BEST1	XM_005274210.5 linkuse as main transcript	c.-373T>A	5_prime_UTR_variant	1/10	XP_005274267.1
BEST1	XM_005274221.5 linkuse as main transcript	c.-373T>A	5_prime_UTR_variant	1/7	XP_005274278.1	B7Z375

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000534553 linkuse as main transcript	c.-548T>A		5_prime_UTR_variant	1/5	2		ENSP00000431189.1		E9PMB5

Frequencies

GnomAD3 genomes

AF:

0.00739

AC:

1124

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00717

GnomAD4 exome

AF:

0.0129

AC:

AN:

310

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

AN XY:

208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00694

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0221

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00737

AC:

1122

AN:

152278

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00746

Hom.:

Bravo

AF:

0.00710

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant vitreoretinochoroidopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Vitelliform macular dystrophy 2

Benign:1

Likely 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

-0.81

CADD

Benign

0.37

DANN

Benign

0.40

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