rs989758

Positions:

• chr5-77249135-G-A
• chr5-77249135-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+37871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,072 control chromosomes in the GnomAD database, including 13,399 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 0.41 (13399 hom., cov: 33)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.339+37871G>A		intron_variant		ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.339+37871G>A		intron_variant		1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62451 AN: 151954 Hom.: 13376 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.411 AC: 62529 AN: 152072 Hom.: 13399 Cov.: 33 AF XY: 0.416 AC XY: 30920 AN XY: 74356

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.422

Alfa AF: 0.380 Hom.: 6109

Bravo AF: 0.418

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.57

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: rs989758; hg19: chr5-76544960;