chr5-77239986-T-G

Variant names:

• chr5-77239986-T-G
• rs2046045
• NM_003719.5:c.339+28722T>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+28722T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,124 control chromosomes in the GnomAD database, including 22,718 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 0.53 (22718 hom., cov: 31)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 31 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 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+28722T>G		intron	N/A	NP_003710.1
	PDE8B	NM_001349749.3		c.339+28722T>G		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.339+28722T>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+28722T>G		intron	N/A	ENSP00000264917.6
	PDE8B	ENST00000342343.8	TSL:1	c.339+28722T>G		intron	N/A	ENSP00000345646.4
	PDE8B	ENST00000340978.7	TSL:1	c.339+28722T>G		intron	N/A	ENSP00000345446.3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79639 AN: 151004 Hom.: 22662 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.528 AC: 79760 AN: 151124 Hom.: 22718 Cov.: 31 AF XY: 0.530 AC XY: 39185 AN XY: 73900

African (AFR) AF: 0.739 AC: 30089 AN: 40712

American (AMR) AF: 0.554 AC: 8414 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4297 AN: 5150

South Asian (SAS) AF: 0.567 AC: 2725 AN: 4810

European-Finnish (FIN) AF: 0.413 AC: 4354 AN: 10534

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26845 AN: 67940

Other (OTH) AF: 0.537 AC: 1128 AN: 2102

Alfa AF: 0.459 Hom.: 31436

Bravo AF: 0.543

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.27
PhyloP100		-1.3
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: rs2046045; hg19: chr5-76535811;