rs12514694

Positions:

• chr5-77295873-G-A

Variant summary

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

The NM_003719.5(PDE8B):​c.340-16121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,130 control chromosomes in the GnomAD database, including 1,219 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 0.12 (1219 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.340-16121G>A		intron_variant		ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.340-16121G>A		intron_variant		1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17775 AN: 152012 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.117 AC: 17771 AN: 152130 Hom.: 1219 Cov.: 32 AF XY: 0.119 AC XY: 8878 AN XY: 74356

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0469

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.125

Alfa AF: 0.124 Hom.: 1651

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.62

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: rs12514694; hg19: chr5-76591698;