chr12-69661130-A-G

Variant names:

• chr12-69661130-A-G
• rs1373453
• NM_032735.3:c.1101-5317T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000279551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032735.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEST3	NM_032735.3	MANE Select	c.1101-5317T>C		intron	N/A	NP_116124.2
	BEST3	NM_001282613.2		c.783-5317T>C		intron	N/A	NP_001269542.1
	BEST3	NM_152439.4		c.462-5317T>C		intron	N/A	NP_689652.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEST3	ENST00000330891.10	TSL:5 MANE Select	c.1101-5317T>C		intron	N/A	ENSP00000332413.5
	BEST3	ENST00000553096.5	TSL:1	c.783-5317T>C		intron	N/A	ENSP00000449548.1
	BEST3	ENST00000488961.5	TSL:1	c.462-5317T>C		intron	N/A	ENSP00000433213.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.223 AC: 9260 AN: 41478

American (AMR) AF: 0.0663 AC: 1015 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5164

South Asian (SAS) AF: 0.104 AC: 504 AN: 4830

European-Finnish (FIN) AF: 0.158 AC: 1671 AN: 10600

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6487 AN: 67996

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.122 Hom.: 1051

Bravo AF: 0.133

Asia WGS AF: 0.151 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1373453; hg19: chr12-70054910;