11-61950135-C-T

Position:

• chr11-61950135-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.194

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 -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST1	NM_001363592.1	c.-329C>T		5_prime_UTR_variant	1/10		NP_001350521.1
BEST1	XM_005274210.5	c.-329C>T		5_prime_UTR_variant	1/10		XP_005274267.1
BEST1	XM_005274221.5	c.-329C>T		5_prime_UTR_variant	1/7		XP_005274278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000534553.5	c.-504C>T		5_prime_UTR_variant	1/5	2		ENSP00000431189

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25535 AN: 152016 Hom.: 3466 Cov.: 32

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: 29 AN: 220 Hom.: 3 Cov.: 0 AF XY: 0.151 AC XY: 22 AN XY: 146

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.: 32 AF XY: 0.179 AC XY: 13297 AN XY: 74386

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

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	12
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

Other links and lift over

dbSNP: rs972354; hg19: chr11-61717607;