rs2928163

Positions:

• chr5-77192420-G-A
• chr5-77192420-G-T

Variant summary

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

The NM_001349750.3(PDE8B):​c.36+11934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,092 control chromosomes in the GnomAD database, including 40,617 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 0.72 (40617 hom., cov: 31)
• Consequence: PDE8B NM_001349750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

Genes affected

ENSG00000284762 (HGNC:):

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_001349750.3	c.36+11934G>A		intron_variant			NP_001336679.1
PDE8B	NM_001376062.1	c.36+11934G>A		intron_variant			NP_001362991.1
PDE8B	NM_001349752.3	c.36+11934G>A		intron_variant			NP_001336681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000284762	ENST00000646262.1	c.-34+73899G>A		intron_variant				ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109688 AN: 151974 Hom.: 40562 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.722 AC: 109803 AN: 152092 Hom.: 40617 Cov.: 31 AF XY: 0.728 AC XY: 54152 AN XY: 74342

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.707

Alfa AF: 0.701 Hom.: 7069

Bravo AF: 0.713

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2928163; hg19: chr5-76488245;