19-10467167-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001111307.2(PDE4A):​c.2207C>T​(p.Ala736Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A736E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

PDE4A
NM_001111307.2 missense

Scores

19

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.041576594).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDE4ANM_001111307.2 linkc.2207C>T p.Ala736Val missense_variant 15/15 ENST00000380702.7 NP_001104777.1 P27815-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDE4AENST00000380702.7 linkc.2207C>T p.Ala736Val missense_variant 15/151 NM_001111307.2 ENSP00000370078.3 P27815-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152060
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251318
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.0000424
AC:
62
AN:
1461870
Hom.:
0
Cov.:
34
AF XY:
0.0000440
AC XY:
32
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152060
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000141
Hom.:
5790
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
0.24
DANN
Benign
0.90
DEOGEN2
Benign
0.032
.;T;.;.;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.71
T;T;T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.042
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;N;.;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.47
.;.;N;N;N
REVEL
Benign
0.036
Sift
Benign
0.48
.;.;T;T;T
Sift4G
Benign
0.26
T;T;T;T;T
Polyphen
0.0040, 0.037, 0.0070, 0.0030
.;B;B;B;B
Vest4
0.035
MVP
0.43
ClinPred
0.015
T
GERP RS
-4.4
Varity_R
0.012

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.

Other links and lift over

dbSNP: rs1051738; hg19: chr19-10577843; API