Variant rs3741755 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032735.3(BEST3):c.636+40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,595,536 control chromosomes in the GnomAD database, including 123,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9491 hom., cov: 31)

Exomes 𝑓: 0.39 ( 114106 hom. )

Consequence

BEST3
NM_032735.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Variant links:

Genes affected

BEST3 (HGNC:17105): (bestrophin 3) BEST3 belongs to the bestrophin family of anion channels, which includes BEST1 (MIM 607854), the gene mutant in vitelliform macular dystrophy (VMD; MIM 153700), and 2 other BEST1-like genes, BEST2 (MIM 607335) and BEST4 (MIM 607336). Bestrophins are transmembrane (TM) proteins that share a homology region containing a high content of aromatic residues, including an invariant arg-phe-pro (RFP) motif. The bestrophin genes share a conserved gene structure, with almost identical sizes of the 8 RFP-TM domain-encoding exons and highly conserved exon-intron boundaries. Each of the 4 bestrophin genes has a unique 3-prime end of variable length (Stohr et al., 2002 [PubMed 12032738]; Tsunenari et al., 2003 [PubMed 12907679]).[supplied by OMIM, Mar 2008]

BEST3 links:

LOC105369823 (HGNC:):

LOC105369823 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST3	NM_032735.3 linkuse as main transcript	c.636+40G>C		intron_variant		ENST00000330891.10	NP_116124.2
LOC105369823	XR_007063357.1 linkuse as main transcript	n.312-9842C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST3	ENST00000330891.10 linkuse as main transcript	c.636+40G>C		intron_variant		5	NM_032735.3	ENSP00000332413	P2	Q8N1M1-2

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52588

AN:

151892

Hom.:

9485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.356

GnomAD3 exomes

AF:

0.390

AC:

96059

AN:

246170

Hom.:

19577

AF XY:

0.405

AC XY:

54069

AN XY:

133570

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.392

AC:

566220

AN:

1443526

Hom.:

114106

Cov.:

AF XY:

0.399

AC XY:

286587

AN XY:

719038

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.566

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.346

AC:

52623

AN:

152010

Hom.:

9491

Cov.:

AF XY:

0.349

AC XY:

25930

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.369

Hom.:

1953

Bravo

AF:

0.333

Asia WGS

AF:

0.373

AC:

1297

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.0

DANN

Benign

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over