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GeneBe

19-10420824-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001111307.2(PDE4A):c.60G>C(p.Arg20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,587,724 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00099 ( 17 hom. )

Consequence

PDE4A
NM_001111307.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.48
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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10420824-G-C is Benign according to our data. Variant chr19-10420824-G-C is described in ClinVar as [Benign]. Clinvar id is 768971.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=2.48 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1134/152270) while in subpopulation AFR AF= 0.0243 (1008/41564). AF 95% confidence interval is 0.023. There are 12 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1126 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE4ANM_001111307.2 linkuse as main transcriptc.60G>C p.Arg20= synonymous_variant 1/15 ENST00000380702.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE4AENST00000380702.7 linkuse as main transcriptc.60G>C p.Arg20= synonymous_variant 1/151 NM_001111307.2 P27815-1
PDE4AENST00000592685.5 linkuse as main transcriptc.254+2959G>C intron_variant 1 P27815-7

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00740
AC:
1126
AN:
152162
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00471
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0159
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00169
AC:
344
AN:
203312
Hom.:
2
AF XY:
0.00125
AC XY:
143
AN XY:
114366
show subpopulations
Gnomad AFR exome
AF:
0.0213
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.000112
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000713
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000394
Gnomad OTH exome
AF:
0.00271
GnomAD4 exome
AF:
0.000995
AC:
1428
AN:
1435454
Hom.:
17
Cov.:
32
AF XY:
0.000958
AC XY:
684
AN XY:
714232
show subpopulations
Gnomad4 AFR exome
AF:
0.0247
Gnomad4 AMR exome
AF:
0.00254
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000711
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000265
Gnomad4 OTH exome
AF:
0.00300
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00745
AC:
1134
AN:
152270
Hom.:
12
Cov.:
32
AF XY:
0.00674
AC XY:
502
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0243
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000485
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00324
Hom.:
0
Bravo
AF:
0.00857
Asia WGS
AF:
0.00203
AC:
8
AN:
3468

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 testingInvitaeAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
8.5
Dann
Benign
0.75

Splicing

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: rs78392044; hg19: chr19-10531500; COSMIC: COSV104420712; COSMIC: COSV104420712; API