5-77219999-A-G

Variant names:

• chr5-77219999-A-G
• rs9687206
• NM_003719.5:c.339+8735A>G

Variant summary

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

The NM_003719.5(PDE8B):​c.339+8735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,026 control chromosomes in the GnomAD database, including 24,416 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 0.55 (24416 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 9 publications found

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]

PDE8B Gene-Disease associations (from GenCC):

• autosomal dominant striatal neurodegeneration type 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pigmented nodular adrenocortical disease, primary, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• primary pigmented nodular adrenocortical disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• striatal degeneration, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PDE8B (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003719.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_003719.5	MANE Select	c.339+8735A>G		intron	N/A	NP_003710.1
	PDE8B	NM_001349749.3		c.339+8735A>G		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.339+8735A>G		intron	N/A	NP_001336677.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.339+8735A>G		intron	N/A	ENSP00000264917.6
	PDE8B	ENST00000342343.8	TSL:1	c.339+8735A>G		intron	N/A	ENSP00000345646.4
	PDE8B	ENST00000340978.7	TSL:1	c.339+8735A>G		intron	N/A	ENSP00000345446.3

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83503 AN: 151908 Hom.: 24366 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.550 AC: 83615 AN: 152026 Hom.: 24416 Cov.: 32 AF XY: 0.553 AC XY: 41087 AN XY: 74306

African (AFR) AF: 0.733 AC: 30380 AN: 41464

American (AMR) AF: 0.566 AC: 8645 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4339 AN: 5170

South Asian (SAS) AF: 0.578 AC: 2785 AN: 4820

European-Finnish (FIN) AF: 0.476 AC: 5033 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29311 AN: 67936

Other (OTH) AF: 0.556 AC: 1173 AN: 2110

Alfa AF: 0.466 Hom.: 28165

Bravo AF: 0.564

Asia WGS AF: 0.691 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.0
DANN	Benign	0.82
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9687206; hg19: chr5-76515824; COSMIC: COSV53746534;