Variant 4-653717-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000283.4(PDE6B):c.712-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 997,264 control chromosomes in the GnomAD database, including 11,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3422 hom., cov: 33)

Exomes 𝑓: 0.13 ( 8178 hom. )

Consequence

PDE6B
NM_000283.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.14

Variant links:

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 links:

PDE6B (HGNC:):

PDE6B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 4-653717-A-G is Benign according to our data. Variant chr4-653717-A-G is described in ClinVar as [Benign]. Clinvar id is 1241227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6B	NM_000283.4 linkuse as main transcript	c.712-135A>G		intron_variant		ENST00000496514.6	NP_000274.3	P35913-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6B	ENST00000496514.6 linkuse as main transcript	c.712-135A>G		intron_variant		1	NM_000283.4	ENSP00000420295.1		P35913-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28050

AN:

152030

Hom.:

3391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0959

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.129

AC:

108789

AN:

845116

Hom.:

8178

Cov.:

AF XY:

0.127

AC XY:

55682

AN XY:

439540

show subpopulations

Gnomad4 AFR exome

AF:

0.336

Gnomad4 AMR exome

AF:

0.0872

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.00243

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.185

AC:

28119

AN:

152148

Hom.:

3422

Cov.:

AF XY:

0.182

AC XY:

13545

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0960

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.0558

Hom.:

Bravo

AF:

0.191

Asia WGS

AF:

0.0810

AC:

283

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Nov 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.63

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over