rs4704397

chr5-77222617-G-Achr5-77222617-G-C

Variant summary

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

The NM_003719.5(PDE8B):c.339+11353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,022 control chromosomes in the GnomAD database, including 25,037 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 0.54 (25037 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.339+11353G>A		intron_variant		ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.339+11353G>A		intron_variant		1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82330 AN: 151904 Hom.: 24981 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.542 AC: 82447 AN: 152022 Hom.: 25037 Cov.: 32 AF XY: 0.544 AC XY: 40405 AN XY: 74290

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.545

Alfa AF: 0.417 Hom.: 25757

Bravo AF: 0.564

Asia WGS AF: 0.684 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.2
Dann	Benign	0.48

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: rs4704397; hg19: chr5-76518442;