rs12514694

Variant names:

• chr5-77295873-G-A
• rs12514694
• NM_003719.5:c.340-16121G>A

Variant summary

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

The NM_003719.5(PDE8B):​c.340-16121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,130 control chromosomes in the GnomAD database, including 1,219 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 0.12 (1219 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 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.340-16121G>A		intron	N/A	NP_003710.1
	PDE8B	NM_001349749.3		c.340-2927G>A		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.340-16124G>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.340-16121G>A		intron	N/A	ENSP00000264917.6
	PDE8B	ENST00000342343.8	TSL:1	c.340-29666G>A		intron	N/A	ENSP00000345646.4
	PDE8B	ENST00000340978.7	TSL:1	c.340-16121G>A		intron	N/A	ENSP00000345446.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17775 AN: 152012 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.117 AC: 17771 AN: 152130 Hom.: 1219 Cov.: 32 AF XY: 0.119 AC XY: 8878 AN XY: 74356

African (AFR) AF: 0.0619 AC: 2570 AN: 41516

American (AMR) AF: 0.140 AC: 2139 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 163 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1499 AN: 5162

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1873 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8717 AN: 67978

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.123 Hom.: 3798

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.62
PhyloP100		-0.59
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: rs12514694; hg19: chr5-76591698;