dbSNP rs12520862: PDE8B:c.339+13423G>T (chr5-77224687-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003719.5(PDE8B):c.339+13423G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,108 control chromosomes in the GnomAD database, including 2,027 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 0.16 ( 2027 hom., cov: 32)

Consequence

PDE8B
NM_003719.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289

Publications

5 publications found

Variant links:

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 links:

PDE8B (HGNC:):

PDE8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5 link	c.339+13423G>T		intron_variant	Intron 1 of 21	ENST00000264917.10	NP_003710.1	O95263-1B3KN77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10 link	c.339+13423G>T		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6		O95263-1
PDE8B	ENST00000646262.1 link	c.-33-87307G>T		intron_variant	Intron 3 of 23			ENSP00000493971.1		A0A2R8Y4E6

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24231

AN:

151990

Hom.:

2022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.164

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

GnomAD4 genome

AF:

0.159

AC:

24245

AN:

152108

Hom.:

2027

Cov.:

AF XY:

0.163

AC XY:

12149

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.163

AC:

6780

AN:

41506

American (AMR)

AF:

0.146

AC:

2232

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3468

East Asian (EAS)

AF:

0.324

AC:

1676

AN:

5168

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4822

European-Finnish (FIN)

AF:

0.188

AC:

1986

AN:

10550

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9572

AN:

67988

Other (OTH)

AF:

0.167

AC:

354

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1060

2120

3180

4240

5300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

2547

Bravo

AF:

0.157

Asia WGS

AF:

0.266

AC:

923

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.37

(source)

DANN

Benign

0.64

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over