rs796538

Variant names:

• chr12-69644728-G-A
• rs796538
• ENST00000331471.8:c.1101-941C>T

Variant summary

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

The ENST00000331471.8(BEST3):​c.1101-941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,052 control chromosomes in the GnomAD database, including 24,873 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 0.56 (24873 hom., cov: 32)
• Consequence: BEST3 ENST00000331471.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEST3	NM_001282614.2	c.1101-941C>T		intron_variant	Intron 9 of 9		NP_001269543.1
LOC105369823	XR_007063357.1	n.311+5714G>A		intron_variant	Intron 3 of 3
LOC105369823	XR_007063358.1	n.311+5714G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEST3	ENST00000331471.8	c.1101-941C>T		intron_variant	Intron 9 of 9	1		ENSP00000329064.4
BEST3	ENST00000547208.5	n.*119-941C>T		intron_variant	Intron 6 of 6	5		ENSP00000449868.1
ENSG00000305711	ENST00000812541.1	n.491+5714G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84656 AN: 151934 Hom.: 24852 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.557 AC: 84729 AN: 152052 Hom.: 24873 Cov.: 32 AF XY: 0.557 AC XY: 41357 AN XY: 74300

African (AFR) AF: 0.733 AC: 30398 AN: 41482

American (AMR) AF: 0.592 AC: 9051 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3868 AN: 5180

South Asian (SAS) AF: 0.423 AC: 2037 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5047 AN: 10528

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30968 AN: 67978

Other (OTH) AF: 0.545 AC: 1149 AN: 2110

Alfa AF: 0.490 Hom.: 35673

Bravo AF: 0.581

Asia WGS AF: 0.601 AC: 2087 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.22
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796538; hg19: chr12-70038508;