Genetic Variant PDE4A:c.*1177T>G (chr19-10468798-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001111307.2(PDE4A):c.*1177T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,790 control chromosomes in the GnomAD database, including 14,765 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 0.43 ( 14689 hom., cov: 29)

Exomes 𝑓: 0.35 ( 76 hom. )

Consequence

PDE4A
NM_001111307.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

19 publications found

Variant links:

Genes affected

PDE4A (HGNC:8780): (phosphodiesterase 4A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 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 described for this gene.[provided by RefSeq, Jul 2011]

PDE4A 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4A	NM_001111307.2 link	c.*1177T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000380702.7	NP_001104777.1	P27815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4A	ENST00000380702.7 link	c.*1177T>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001111307.2	ENSP00000370078.3		P27815-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64882

AN:

151590

Hom.:

14663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.579

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.350

AC:

379

AN:

1082

Hom.:

Cov.:

AF XY:

0.358

AC XY:

263

AN XY:

734

show subpopulations

African (AFR)

AF:

0.556

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.433

AC:

AN:

150

South Asian (SAS)

AF:

0.222

AC:

AN:

European-Finnish (FIN)

AF:

0.291

AC:

127

AN:

436

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.368

AC:

154

AN:

418

Other (OTH)

AF:

0.393

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.428

AC:

64953

AN:

151708

Hom.:

14689

Cov.:

AF XY:

0.425

AC XY:

31494

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.579

AC:

23916

AN:

41312

American (AMR)

AF:

0.429

AC:

6520

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3468

East Asian (EAS)

AF:

0.489

AC:

2514

AN:

5138

South Asian (SAS)

AF:

0.329

AC:

1584

AN:

4808

European-Finnish (FIN)

AF:

0.316

AC:

3327

AN:

10540

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.361

AC:

24526

AN:

67918

Other (OTH)

AF:

0.408

AC:

860

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1781

3562

5342

7123

8904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.368

Hom.:

17821

Bravo

AF:

0.448

Asia WGS

AF:

0.394

AC:

1368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.078

(source)

DANN

Benign

0.30

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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