rs2668898

chr11-61958026-A-Gchr11-61958026-A-T

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.715-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,520,098 control chromosomes in the GnomAD database, including 98,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (13423 hom., cov: 32)
  • Exomes 𝑓: 0.32 (85485 hom.)
• Consequence: BEST1 NM_004183.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.22

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]

LOC107984334 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-61958026-A-G is Benign according to our data. Variant chr11-61958026-A-G is described in ClinVar as [Benign]. Clinvar id is 1281169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEST1	NM_004183.4	c.715-120A>G		intron_variant		ENST00000378043.9
LOC107984334	XR_001748245.2	n.668T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEST1	ENST00000378043.9	c.715-120A>G		intron_variant		1	NM_004183.4	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58924 AN: 151836 Hom.: 13416 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.319 AC: 436446 AN: 1368144 Hom.: 85485 AF XY: 0.327 AC XY: 223859 AN XY: 684508

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.913

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.388 AC: 58973 AN: 151954 Hom.: 13423 Cov.: 32 AF XY: 0.402 AC XY: 29845 AN XY: 74244

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.323

Alfa AF: 0.277 Hom.: 1167

Bravo AF: 0.390

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

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.61
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2668898; hg19: chr11-61725498;