rs11609972

Variant names:

• chr12-69677113-C-T
• rs11609972
• NM_032735.3:c.715-45G>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.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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEST3	NM_032735.3	MANE Select	c.715-45G>A		intron	N/A	NP_116124.2
	BEST3	NM_001282613.2		c.397-45G>A		intron	N/A	NP_001269542.1
	BEST3	NM_152439.4		c.228+67G>A		intron	N/A	NP_689652.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEST3	ENST00000330891.10	TSL:5 MANE Select	c.715-45G>A		intron	N/A	ENSP00000332413.5
	BEST3	ENST00000553096.5	TSL:1	c.397-45G>A		intron	N/A	ENSP00000449548.1
	BEST3	ENST00000488961.5	TSL:1	c.228+67G>A		intron	N/A	ENSP00000433213.1

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

GnomAD2 exomes AF: 0.0254 AC: 6308 AN: 248424 AF XY: 0.0264

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 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

African (AFR) AF: 0.0717 AC: 2401 AN: 33472

American (AMR) AF: 0.00959 AC: 429 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 857 AN: 26130

East Asian (EAS) AF: 0.000781 AC: 31 AN: 39682

South Asian (SAS) AF: 0.0445 AC: 3837 AN: 86246

European-Finnish (FIN) AF: 0.00833 AC: 445 AN: 53394

Middle Eastern (MID) AF: 0.0342 AC: 197 AN: 5768

European-Non Finnish (NFE) AF: 0.0292 AC: 32506 AN: 1111786

Other (OTH) AF: 0.0300 AC: 1811 AN: 60390

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

African (AFR) AF: 0.0718 AC: 2982 AN: 41524

American (AMR) AF: 0.0203 AC: 311 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0496 AC: 239 AN: 4816

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0274 AC: 1867 AN: 68028

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0337 Hom.: 36

Bravo AF: 0.0397

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		0.32
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: rs11609972; hg19: chr12-70070893;