5-77239986-T-G

Position:

• chr5-77239986-T-G

Variant summary

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

The NM_003719.5(PDE8B):​c.339+28722T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,124 control chromosomes in the GnomAD database, including 22,718 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 0.53 (22718 hom., cov: 31)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

PDE8B (HGNC:8794): (phosphodiesterase 8B) The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.339+28722T>G		intron_variant		ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.339+28722T>G		intron_variant		1	NM_003719.5	ENSP00000264917	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79639 AN: 151004 Hom.: 22662 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.528 AC: 79760 AN: 151124 Hom.: 22718 Cov.: 31 AF XY: 0.530 AC XY: 39185 AN XY: 73900

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.537

Alfa AF: 0.430 Hom.: 12831

Bravo AF: 0.543

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.27

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: rs2046045; hg19: chr5-76535811;