4-653813-G-A

Position:

• chr4-653813-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000283.4(PDE6B):​c.712-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,611,514 control chromosomes in the GnomAD database, including 573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (303 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (270 hom.)
• Consequence: PDE6B NM_000283.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516

Genes affected

PDE6B (HGNC:8786): (phosphodiesterase 6B) Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

PDE6B-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-653813-G-A is Benign according to our data. Variant chr4-653813-G-A is described in ClinVar as [Benign]. Clinvar id is 1293515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6B	NM_000283.4	c.712-39G>A		intron_variant		ENST00000496514.6	NP_000274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6B	ENST00000496514.6	c.712-39G>A		intron_variant		1	NM_000283.4	ENSP00000420295.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5342 AN: 152176 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0112 AC: 2799 AN: 249536 Hom.: 127 AF XY: 0.00886 AC XY: 1200 AN XY: 135378

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.00903

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00637

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00285

Gnomad OTH exome AF: 0.00987

GnomAD4 exome AF: 0.00587 AC: 8561 AN: 1459220 Hom.: 270 Cov.: 31 AF XY: 0.00548 AC XY: 3981 AN XY: 726100

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.00982

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00702

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0352 AC: 5362 AN: 152294 Hom.: 303 Cov.: 33 AF XY: 0.0334 AC XY: 2490 AN XY: 74474

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0173 Hom.: 18

Bravo AF: 0.0399

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.75
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28514424; hg19: chr4-647602;