Genetic Variant 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:

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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=-0.84).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002605.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDE8A	NM_002605.3	MANE Select	c.853-196T>C	intron	N/A	NP_002596.1
PDE8A	NM_173454.1		c.715-196T>C	intron	N/A	NP_775656.1
PDE8A	NM_001243137.2		c.637-196T>C	intron	N/A	NP_001230066.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.853-196T>C	intron	N/A	ENSP00000378056.1
PDE8A	ENST00000310298.8	TSL:1	c.853-196T>C	intron	N/A	ENSP00000311453.4
PDE8A	ENST00000339708.9	TSL:1	c.715-196T>C	intron	N/A	ENSP00000340679.5

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over