dbSNP rs6887019: PDE8B:c.709-2263T>C (chr5-77334964-T-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.709-2263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,050 control chromosomes in the GnomAD database, including 17,399 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 0.47 ( 17399 hom., cov: 33)

Consequence

PDE8B
NM_003719.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

2 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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5 link	c.709-2263T>C		intron_variant	Intron 5 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.709-2263T>C		intron_variant	Intron 5 of 21	1	NM_003719.5	ENSP00000264917.6		O95263-1
PDE8B	ENST00000646262.1 link	c.337-2263T>C		intron_variant	Intron 7 of 23			ENSP00000493971.1		A0A2R8Y4E6

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71792

AN:

151932

Hom.:

17389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.470

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

GnomAD4 genome

AF:

0.472

AC:

71841

AN:

152050

Hom.:

17399

Cov.:

AF XY:

0.472

AC XY:

35098

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.551

AC:

22828

AN:

41466

American (AMR)

AF:

0.418

AC:

6388

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1191

AN:

3464

East Asian (EAS)

AF:

0.384

AC:

1982

AN:

5164

South Asian (SAS)

AF:

0.351

AC:

1693

AN:

4824

European-Finnish (FIN)

AF:

0.512

AC:

5400

AN:

10552

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30762

AN:

67972

Other (OTH)

AF:

0.467

AC:

986

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1932

3864

5796

7728

9660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.474

Hom.:

2270

Bravo

AF:

0.468

Asia WGS

AF:

0.390

AC:

1354

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.42

(source)

DANN

Benign

0.48

PhyloP100

-1.7

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