Variant rs1051738 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001111307.2(PDE4A):c.2207C>A(p.Ala736Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,952 control chromosomes in the GnomAD database, including 27,859 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3433 hom., cov: 31)

Exomes 𝑓: 0.18 ( 24426 hom. )

Consequence

PDE4A
NM_001111307.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049764514).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4A	NM_001111307.2 linkuse as main transcript	c.2207C>A	p.Ala736Glu	missense_variant	15/15	ENST00000380702.7	NP_001104777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4A	ENST00000380702.7 linkuse as main transcript	c.2207C>A	p.Ala736Glu	missense_variant	15/15	1	NM_001111307.2	ENSP00000370078		P27815-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30746

AN:

152026

Hom.:

3426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.169

AC:

42579

AN:

251318

Hom.:

3850

AF XY:

0.168

AC XY:

22872

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.179

AC:

261775

AN:

1461808

Hom.:

24426

Cov.:

AF XY:

0.178

AC XY:

129351

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.0984

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.202

AC:

30774

AN:

152144

Hom.:

3433

Cov.:

AF XY:

0.198

AC XY:

14761

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.179

Hom.:

5790

Bravo

AF:

0.209

TwinsUK

AF:

0.183

AC:

678

ALSPAC

AF:

0.188

AC:

723

ESP6500AA

AF:

0.286

AC:

1259

ESP6500EA

AF:

0.179

AC:

1536

ExAC

AF:

0.176

AC:

21416

Asia WGS

AF:

0.127

AC:

440

AN:

3478

EpiCase

AF:

0.188

EpiControl

AF:

0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.1

DANN

Benign

0.88

DEOGEN2

Benign

0.027

.;T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.76

T;T;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

0.070

.;.;N;N;N

REVEL

Benign

0.043

Sift

Uncertain

0.021

.;.;D;D;D

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.22, 0.85, 0.71, 0.52

.;B;P;P;P

Vest4

0.040

ClinPred

0.0075

GERP RS

-4.4

Varity_R

0.073

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over