5-77369359-G-A

Position:

• chr5-77369359-G-A

Variant summary

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

The ENST00000264917.10(PDE8B):​c.1167+15953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,004 control chromosomes in the GnomAD database, including 3,333 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 0.19 (3333 hom., cov: 30)
• Consequence: PDE8B ENST00000264917.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.1167+15953G>A		intron_variant		ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.1167+15953G>A		intron_variant		1	NM_003719.5	ENSP00000264917	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28558 AN: 151888 Hom.: 3331 Cov.: 30

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.188 AC: 28561 AN: 152004 Hom.: 3333 Cov.: 30 AF XY: 0.188 AC XY: 13978 AN XY: 74282

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.200

Alfa AF: 0.240 Hom.: 2194

Bravo AF: 0.174

Asia WGS AF: 0.173 AC: 603 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	4.6
DANN	Benign	0.55

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: rs10514096; hg19: chr5-76665184;