12-69667006-G-T

Variant names:

• chr12-69667006-G-T
• rs7310083
• NM_032735.3:c.1100+4422C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032735.3(BEST3):​c.1100+4422C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,104 control chromosomes in the GnomAD database, including 1,256 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 0.11 (1256 hom., cov: 32)
• Consequence: BEST3 NM_032735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 1 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]

ENSG00000305711 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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.1100+4422C>A		intron	N/A	NP_116124.2
	BEST3	NM_001282613.2		c.782+4422C>A		intron	N/A	NP_001269542.1
	BEST3	NM_152439.4		c.461+4422C>A		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.1100+4422C>A		intron	N/A	ENSP00000332413.5
	BEST3	ENST00000553096.5	TSL:1	c.782+4422C>A		intron	N/A	ENSP00000449548.1
	BEST3	ENST00000488961.5	TSL:1	c.461+4422C>A		intron	N/A	ENSP00000433213.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16101 AN: 151986 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16129 AN: 152104 Hom.: 1256 Cov.: 32 AF XY: 0.104 AC XY: 7759 AN XY: 74358

African (AFR) AF: 0.220 AC: 9107 AN: 41448

American (AMR) AF: 0.105 AC: 1611 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.0530 AC: 274 AN: 5168

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4822

European-Finnish (FIN) AF: 0.0244 AC: 258 AN: 10582

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3795 AN: 68012

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.0744 Hom.: 2035

Bravo AF: 0.118

Asia WGS AF: 0.0740 AC: 261 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.54
DANN	Benign	0.45
PhyloP100		-0.46
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: rs7310083; hg19: chr12-70060786;