rs1373453

chr12-69661130-A-G

Variant summary

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

The NM_032735.3(BEST3):c.1101-5317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,156 control chromosomes in the GnomAD database, including 1,669 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 0.14 (1669 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: BEST3 NM_032735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEST3	NM_032735.3	c.1101-5317T>C		intron_variant		ENST00000330891.10
LOC105369823	XR_007063357.1	n.311+22116A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEST3	ENST00000330891.10	c.1101-5317T>C		intron_variant		5	NM_032735.3	P2
	ENST00000622965.1	n.300T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20551 AN: 152034 Hom.: 1674 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.135 AC: 20545 AN: 152154 Hom.: 1669 Cov.: 32 AF XY: 0.136 AC XY: 10093 AN XY: 74392

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0663

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.0954

Gnomad4 OTH AF: 0.103

Alfa AF: 0.104 Hom.: 449

Bravo AF: 0.133

Asia WGS AF: 0.151 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	10
Dann	Benign	0.94

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: rs1373453; hg19: chr12-70054910;