5-77166328-C-G

Variant names:

• chr5-77166328-C-G
• rs4361497
• ENST00000646262.1:c.-34+47807C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000646262.1(PDE8B):​c.-34+47807C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,898 control chromosomes in the GnomAD database, including 44,706 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 0.76 (44706 hom., cov: 29)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801
• Publications: 3 publications found

Genes affected

PDE8B (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]

ZBED3-AS1 (HGNC:44188): (ZBED3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-34+47807C>G		intron_variant	Intron 2 of 22		NP_001401551.1
PDE8B	NM_001414623.1	c.-34+47807C>G		intron_variant	Intron 3 of 23		NP_001401552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000646262.1	c.-34+47807C>G		intron_variant	Intron 3 of 23			ENSP00000493971.1
ZBED3-AS1	ENST00000508401.1	n.341-340C>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115595 AN: 151780 Hom.: 44661 Cov.: 29

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.762 AC: 115694 AN: 151898 Hom.: 44706 Cov.: 29 AF XY: 0.769 AC XY: 57097 AN XY: 74242

African (AFR) AF: 0.867 AC: 35908 AN: 41408

American (AMR) AF: 0.652 AC: 9962 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3466

East Asian (EAS) AF: 0.932 AC: 4817 AN: 5170

South Asian (SAS) AF: 0.826 AC: 3971 AN: 4808

European-Finnish (FIN) AF: 0.836 AC: 8803 AN: 10526

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47432 AN: 67930

Other (OTH) AF: 0.747 AC: 1577 AN: 2110

Alfa AF: 0.744 Hom.: 5266

Bravo AF: 0.750

Asia WGS AF: 0.886 AC: 3082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.31
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs4361497; hg19: chr5-76462153;