4-653714-G-C

Position:

• chr4-653714-G-C

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.712-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 982,558 control chromosomes in the GnomAD database, including 5,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1017 hom., cov: 33)
  • Exomes 𝑓: 0.096 (4237 hom.)
• Consequence: PDE6B NM_000283.4 intron
• Scores: Splicing: ADA: 0.00003223
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.413

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-653714-G-C is Benign according to our data. Variant chr4-653714-G-C is described in ClinVar as [Benign]. Clinvar id is 1241108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6B	NM_000283.4	c.712-138G>C		intron_variant		ENST00000496514.6	NP_000274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6B	ENST00000496514.6	c.712-138G>C		intron_variant		1	NM_000283.4	ENSP00000420295.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16597 AN: 152096 Hom.: 1015 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0964 AC: 80085 AN: 830344 Hom.: 4237 Cov.: 11 AF XY: 0.0957 AC XY: 41319 AN XY: 431904

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0659

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.00222

Gnomad4 SAS exome AF: 0.0821

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.109 AC: 16613 AN: 152214 Hom.: 1017 Cov.: 33 AF XY: 0.110 AC XY: 8194 AN XY: 74404

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.105 Hom.: 113

Bravo AF: 0.107

Asia WGS AF: 0.0580 AC: 202 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	-0.95
CADD	Benign	4.6
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs28569875; hg19: chr4-647503;