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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE4A	NM_001111307.2	MANE Select	c.*1177T>G	3_prime_UTR	Exon 15 of 15	NP_001104777.1	P27815-1
PDE4A	NM_001243121.2		c.*1177T>G	3_prime_UTR	Exon 17 of 17	NP_001230050.1	P27815-7
PDE4A	NM_001111308.1		c.*1177T>G	3_prime_UTR	Exon 15 of 15	NP_001104778.1	P27815-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.*1177T>G		3_prime_UTR	Exon 15 of 15	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over