11-61951554-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004183.4(BEST1):c.-36-217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,198 control chromosomes in the GnomAD database, including 1,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (1000 hom., cov: 32)
• Consequence: BEST1 NM_004183.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0320

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-61951554-G-A is Benign according to our data. Variant chr11-61951554-G-A is described in ClinVar as [Benign]. Clinvar id is 1276627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEST1	NM_004183.4	c.-36-217G>A		intron_variant		ENST00000378043.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEST1	ENST00000378043.9	c.-36-217G>A		intron_variant		1	NM_004183.4	P1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9413 AN: 152080 Hom.: 1001 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0749

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0618 AC: 9407 AN: 152198 Hom.: 1000 Cov.: 32 AF XY: 0.0668 AC XY: 4971 AN XY: 74394

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0736

Alfa AF: 0.0444 Hom.: 32

Bravo AF: 0.0712

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.4
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

Other links and lift over

dbSNP: rs2736596; hg19: chr11-61719026;