Genetic Variant PDE8B:c.339+10893G>C (chr5-77222157-G-C) – 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+10893G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,250 control chromosomes in the GnomAD database, including 1,100 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 0.10 ( 1100 hom., cov: 32)

Consequence

PDE8B
NM_003719.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.981

Publications

6 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5 link	c.339+10893G>C		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+10893G>C		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6		O95263-1
PDE8B	ENST00000646262.1 link	c.-33-89837G>C		intron_variant	Intron 3 of 23			ENSP00000493971.1		A0A2R8Y4E6

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15499

AN:

152132

Hom.:

1101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0841

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.107

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

GnomAD4 genome

AF:

0.102

AC:

15502

AN:

152250

Hom.:

1100

Cov.:

AF XY:

0.101

AC XY:

7531

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0267

AC:

1111

AN:

41562

American (AMR)

AF:

0.186

AC:

2840

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

531

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.0840

AC:

405

AN:

4822

European-Finnish (FIN)

AF:

0.125

AC:

1329

AN:

10604

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8952

AN:

67996

Other (OTH)

AF:

0.106

AC:

225

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

693

1386

2080

2773

3466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0704

Hom.:

106

Bravo

AF:

0.100

Asia WGS

AF:

0.0420

AC:

148

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.3

(source)

DANN

Benign

0.53

PhyloP100

0.98

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