rs79008179

Variant names:

• chr5-77408888-G-A
• rs79008179
• NM_003719.5:c.1366-5G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003719.5(PDE8B):​c.1366-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,609,390 control chromosomes in the GnomAD database, including 772 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (49 hom., cov: 32)
  • Exomes 𝑓: 0.029 (723 hom.)
• Consequence: PDE8B NM_003719.5 splice_region, intron
• Scores: Splicing: ADA: 0.00005541
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.416

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]

ENSG00000284762 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-77408888-G-A is Benign according to our data. Variant chr5-77408888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 354162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-77408888-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0242 (3687/152268) while in subpopulation NFE AF= 0.0334 (2272/68034). AF 95% confidence interval is 0.0323. There are 49 homozygotes in gnomad4. There are 1757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3687 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.1366-5G>A		splice_region_variant, intron_variant	Intron 13 of 21	ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.1366-5G>A		splice_region_variant, intron_variant	Intron 13 of 21	1	NM_003719.5	ENSP00000264917.6
ENSG00000284762	ENST00000646262.1	c.994-5G>A		splice_region_variant, intron_variant	Intron 15 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3689 AN: 152150 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.0224 AC: 5622 AN: 251310 Hom.: 89 AF XY: 0.0224 AC XY: 3041 AN XY: 135844

Gnomad AFR exome AF: 0.0199

Gnomad AMR exome AF: 0.00700

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00519

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0287 AC: 41854 AN: 1457122 Hom.: 723 Cov.: 30 AF XY: 0.0281 AC XY: 20396 AN XY: 725272

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.00747

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00530

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0243

GnomAD4 genome AF: 0.0242 AC: 3687 AN: 152268 Hom.: 49 Cov.: 32 AF XY: 0.0236 AC XY: 1757 AN XY: 74448

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0305 Hom.: 38

Bravo AF: 0.0235

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency. Insufficient evidence for gene-disease association. -

Autosomal dominant striatal neurodegeneration type 1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

PDE8B-related disorder Benign:1

Sep 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.080
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: rs79008179; hg19: chr5-76704713;