rs11609972

Positions:

• chr12-69677113-C-T

Variant summary

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

The NM_032735.3(BEST3):​c.715-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,613,842 control chromosomes in the GnomAD database, including 930 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 0.037 (166 hom., cov: 32)
  • Exomes 𝑓: 0.029 (764 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST3	NM_032735.3	c.715-45G>A		intron_variant		ENST00000330891.10	NP_116124.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST3	ENST00000330891.10	c.715-45G>A		intron_variant		5	NM_032735.3	ENSP00000332413.5

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5687 AN: 152140 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0254 AC: 6308 AN: 248424 Hom.: 128 AF XY: 0.0264 AC XY: 3561 AN XY: 134876

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0316

Gnomad EAS exome AF: 0.00229

Gnomad SAS exome AF: 0.0451

Gnomad FIN exome AF: 0.00715

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0206

GnomAD4 exome AF: 0.0291 AC: 42514 AN: 1461584 Hom.: 764 Cov.: 31 AF XY: 0.0294 AC XY: 21351 AN XY: 727112

Gnomad4 AFR exome AF: 0.0717

Gnomad4 AMR exome AF: 0.00959

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.000781

Gnomad4 SAS exome AF: 0.0445

Gnomad4 FIN exome AF: 0.00833

Gnomad4 NFE exome AF: 0.0292

Gnomad4 OTH exome AF: 0.0300

GnomAD4 genome AF: 0.0374 AC: 5688 AN: 152258 Hom.: 166 Cov.: 32 AF XY: 0.0353 AC XY: 2626 AN XY: 74456

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0496

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0330 Hom.: 34

Bravo AF: 0.0397

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.69

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: rs11609972; hg19: chr12-70070893;