dbSNP rs2304418: PDE8A:c.853-196T>C (chr15-85097752-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_002605.3(PDE8A):c.853-196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 551,636 control chromosomes in the GnomAD database, including 18,614 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 0.21 ( 4301 hom., cov: 32)

Exomes 𝑓: 0.25 ( 14313 hom. )

Consequence

PDE8A
NM_002605.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.626

Publications

7 publications found

Variant links:

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

PDE8A 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3 link	c.853-196T>C		intron_variant	Intron 8 of 21	ENST00000394553.6	NP_002596.1	O60658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6 link	c.853-196T>C		intron_variant	Intron 8 of 21	1	NM_002605.3	ENSP00000378056.1		O60658-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31551

AN:

152088

Hom.:

4309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0490

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.252

AC:

100714

AN:

399428

Hom.:

14313

AF XY:

0.249

AC XY:

52826

AN XY:

211818

show subpopulations

African (AFR)

AF:

0.0494

AC:

543

AN:

10994

American (AMR)

AF:

0.177

AC:

2656

AN:

14988

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

4303

AN:

12106

East Asian (EAS)

AF:

0.0379

AC:

1005

AN:

26524

South Asian (SAS)

AF:

0.158

AC:

6470

AN:

40926

European-Finnish (FIN)

AF:

0.288

AC:

8635

AN:

29964

Middle Eastern (MID)

AF:

0.353

AC:

610

AN:

1730

European-Non Finnish (NFE)

AF:

0.296

AC:

70792

AN:

239430

Other (OTH)

AF:

0.250

AC:

5700

AN:

22766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3458

6915

10373

13830

17288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31524

AN:

152208

Hom.:

4301

Cov.:

AF XY:

0.206

AC XY:

15324

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0489

AC:

2035

AN:

41576

American (AMR)

AF:

0.204

AC:

3117

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3466

East Asian (EAS)

AF:

0.0520

AC:

269

AN:

5176

South Asian (SAS)

AF:

0.152

AC:

733

AN:

4832

European-Finnish (FIN)

AF:

0.300

AC:

3180

AN:

10584

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19981

AN:

67980

Other (OTH)

AF:

0.241

AC:

507

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1231

2462

3693

4924

6155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.264

Hom.:

3049

Bravo

AF:

0.194

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.1

(source)

DANN

Benign

0.81

PhyloP100

0.63

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over