rs6885813

Variant names:

• chr5-77273786-C-A
• rs6885813
• NM_003719.5:c.340-38208C>A

Variant summary

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

The NM_001349749.3(PDE8B):​c.340-25014C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,830 control chromosomes in the GnomAD database, including 4,542 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 0.22 (4542 hom., cov: 32)
• Consequence: PDE8B NM_001349749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349749.3. 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.340-38208C>A		intron	N/A	NP_003710.1
	PDE8B	NM_001349749.3		c.340-25014C>A		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.340-38211C>A		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.340-38208C>A		intron	N/A	ENSP00000264917.6
	PDE8B	ENST00000342343.8	TSL:1	c.340-51753C>A		intron	N/A	ENSP00000345646.4
	PDE8B	ENST00000340978.7	TSL:1	c.340-38208C>A		intron	N/A	ENSP00000345446.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32920 AN: 151714 Hom.: 4535 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.217 AC: 32938 AN: 151830 Hom.: 4542 Cov.: 32 AF XY: 0.222 AC XY: 16484 AN XY: 74194

African (AFR) AF: 0.0708 AC: 2935 AN: 41426

American (AMR) AF: 0.322 AC: 4921 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3464

East Asian (EAS) AF: 0.443 AC: 2283 AN: 5150

South Asian (SAS) AF: 0.446 AC: 2137 AN: 4788

European-Finnish (FIN) AF: 0.210 AC: 2203 AN: 10500

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16551 AN: 67928

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.240 Hom.: 10857

Bravo AF: 0.215

Asia WGS AF: 0.399 AC: 1388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.32
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6885813; hg19: chr5-76569611;