rs3741755

chr12-69678699-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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]

LOC105369823 (HGNC:):

ACMG classification

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	UniProt
BEST3	NM_032735.3	c.636+40G>C		intron_variant		ENST00000330891.10
LOC105369823	XR_007063357.1	n.312-9842C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEST3	ENST00000330891.10	c.636+40G>C		intron_variant		5	NM_032735.3	P2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52588 AN: 151892 Hom.: 9485 Cov.: 31

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

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.: 26 AF XY: 0.399 AC XY: 286587 AN XY: 719038

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.: 31 AF XY: 0.349 AC XY: 25930 AN XY: 74284

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

Other links and lift over

dbSNP: rs3741755; hg19: chr12-70072479; COSMIC: COSV56994097; COSMIC: COSV56994097;