11-61958127-A-ATCCTCCTCC

Position:

• chr11-61958127-A-ATCCTCCTCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004183.4(BEST1):​c.715-12_715-4dupTCCTCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,544,446 control chromosomes in the GnomAD database, including 560,870 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64168 hom., cov: 0)
  • Exomes 𝑓: 0.85 (496702 hom.)
• Consequence: BEST1 NM_004183.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.82

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 -16 ACMG points.

• BP6: Variant 11-61958127-A-ATCCTCCTCC is Benign according to our data. Variant chr11-61958127-A-ATCCTCCTCC is described in ClinVar as [Likely_benign]. Clinvar id is 166753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST1	NM_004183.4	c.715-12_715-4dupTCCTCCTCC		splice_region_variant, intron_variant		ENST00000378043.9	NP_004174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000378043.9	c.715-12_715-4dupTCCTCCTCC		splice_region_variant, intron_variant		1	NM_004183.4	ENSP00000367282.4

Frequencies

GnomAD3 genomes AF: 0.921 AC: 139222 AN: 151124 Hom.: 64132 Cov.: 0

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.924

GnomAD4 exome AF: 0.853 AC: 1188402 AN: 1393208 Hom.: 496702 Cov.: 82 AF XY: 0.854 AC XY: 592245 AN XY: 693658

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.911

Gnomad4 SAS exome AF: 0.879

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.853

GnomAD4 genome AF: 0.921 AC: 139313 AN: 151238 Hom.: 64168 Cov.: 0 AF XY: 0.921 AC XY: 68090 AN XY: 73892

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.922

Alfa AF: 0.826 Hom.: 4495

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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)	Apr 16, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 16, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1805182; hg19: chr11-61725599;