rs6885813

chr5-77273786-C-A

Variant summary

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

The NM_003719.5(PDE8B):c.340-38208C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,830 control chromosomes in the GnomAD database, including 4,542 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 0.22 (4542 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.340-38208C>A		intron_variant		ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.340-38208C>A		intron_variant		1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32920 AN: 151714 Hom.: 4535 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.217 AC: 32938 AN: 151830 Hom.: 4542 Cov.: 32 AF XY: 0.222 AC XY: 16484 AN XY: 74194

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.233

Alfa AF: 0.252 Hom.: 7645

Bravo AF: 0.215

Asia WGS AF: 0.399 AC: 1388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.55
Dann	Benign	0.32

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: rs6885813; hg19: chr5-76569611;