17-81652196-C-T

Position:

• chr17-81652196-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002602.4(PDE6G):​c.147-511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 150,982 control chromosomes in the GnomAD database, including 15,533 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 0.44 (15533 hom., cov: 32)
• Consequence: PDE6G NM_002602.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

Genes affected

PDE6G (HGNC:8789): (phosphodiesterase 6G) This gene encodes the gamma subunit of cyclic GMP-phosphodiesterase, which is composed of alpha- and beta- catalytic subunits and two identical, inhibitory gamma subunits. This gene is expressed in rod photoreceptors and functions in the phototransduction signaling cascade. It is also expressed in a variety of other tissues, and has been shown to regulate the c-Src protein kinase and G-protein-coupled receptor kinase 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE6G	NM_002602.4	c.147-511G>A		intron_variant		ENST00000331056.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6G	ENST00000331056.10	c.147-511G>A		intron_variant		1	NM_002602.4	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66074 AN: 150858 Hom.: 15498 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.438 AC: 66151 AN: 150982 Hom.: 15533 Cov.: 32 AF XY: 0.443 AC XY: 32652 AN XY: 73726

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.426

Alfa AF: 0.396 Hom.: 3095

Bravo AF: 0.460

Asia WGS AF: 0.699 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7406828; hg19: chr17-79619226;