rs4704389

Variant names:

• chr5-77150278-A-G
• rs4704389
• ENST00000646262.1:c.-34+31757A>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+31757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,018 control chromosomes in the GnomAD database, including 22,624 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 0.52 (22624 hom., cov: 32)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-34+31757A>G		intron_variant	Intron 2 of 22		NP_001401551.1
PDE8B	NM_001414623.1	c.-34+31757A>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+31757A>G		intron_variant	Intron 3 of 23			ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.*86-946A>G		intron_variant	Intron 14 of 15			ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79539 AN: 151898 Hom.: 22613 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.523 AC: 79561 AN: 152018 Hom.: 22624 Cov.: 32 AF XY: 0.532 AC XY: 39532 AN XY: 74302

African (AFR) AF: 0.287 AC: 11921 AN: 41478

American (AMR) AF: 0.556 AC: 8491 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2091 AN: 3472

East Asian (EAS) AF: 0.877 AC: 4528 AN: 5162

South Asian (SAS) AF: 0.636 AC: 3061 AN: 4816

European-Finnish (FIN) AF: 0.627 AC: 6615 AN: 10552

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40913 AN: 67958

Other (OTH) AF: 0.548 AC: 1154 AN: 2104

Alfa AF: 0.557 Hom.: 7899

Bravo AF: 0.506

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.48
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs4704389; hg19: chr5-76446103;