rs4457053

Positions:

• chr5-77129124-G-A
• chr5-77129124-G-T

Variant summary

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

The NM_001414622.1(PDE8B):​c.-34+10603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,998 control chromosomes in the GnomAD database, including 42,433 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 0.74 (42433 hom., cov: 30)
• Consequence: PDE8B NM_001414622.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-34+10603G>A		intron_variant			NP_001401551.1
PDE8B	NM_001414623.1	c.-34+10603G>A		intron_variant			NP_001401552.1
ZBED3-AS1	NR_024398.2	n.525+10603G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000284762	ENST00000646262.1	c.-34+10603G>A		intron_variant				ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.*85+10603G>A		intron_variant				ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112882 AN: 151880 Hom.: 42392 Cov.: 30

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.743 AC: 112980 AN: 151998 Hom.: 42433 Cov.: 30 AF XY: 0.749 AC XY: 55609 AN XY: 74264

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.717

Alfa AF: 0.697 Hom.: 48114

Bravo AF: 0.735

Asia WGS AF: 0.858 AC: 2980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4457053; hg19: chr5-76424949;