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GeneBe

19-10454882-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001111307.2(PDE4A):c.837C>T(p.Ser279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,614,060 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 107 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 90 hom. )

Consequence

PDE4A
NM_001111307.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.56
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10454882-C-T is Benign according to our data. Variant chr19-10454882-C-T is described in ClinVar as [Benign]. Clinvar id is 769956.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.56 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE4ANM_001111307.2 linkuse as main transcriptc.837C>T p.Ser279= synonymous_variant 7/15 ENST00000380702.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE4AENST00000380702.7 linkuse as main transcriptc.837C>T p.Ser279= synonymous_variant 7/151 NM_001111307.2 P27815-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0196
AC:
2982
AN:
152104
Hom.:
107
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0679
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00858
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00526
AC:
1322
AN:
251492
Hom.:
36
AF XY:
0.00382
AC XY:
519
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.0696
Gnomad AMR exome
AF:
0.00416
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00202
AC:
2948
AN:
1461838
Hom.:
90
Cov.:
31
AF XY:
0.00175
AC XY:
1273
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.0700
Gnomad4 AMR exome
AF:
0.00465
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.000393
Gnomad4 NFE exome
AF:
0.000121
Gnomad4 OTH exome
AF:
0.00371
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0196
AC:
2978
AN:
152222
Hom.:
107
Cov.:
32
AF XY:
0.0190
AC XY:
1414
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0676
Gnomad4 AMR
AF:
0.00857
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00803
Alfa
AF:
0.00975
Hom.:
12
Bravo
AF:
0.0225
Asia WGS
AF:
0.00404
AC:
14
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
8.3
Dann
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs62639961; hg19: chr19-10565558; COSMIC: COSV104540881; COSMIC: COSV104540881; API