rs27727

Variant summary

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

The NM_001104631.2(PDE4D):​c.648-11020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,044 control chromosomes in the GnomAD database, including 9,280 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 0.34 ( 9280 hom., cov: 32)

Consequence

PDE4D
NM_001104631.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.669
Variant links:
Genes affected
PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE4DNM_001104631.2 linkuse as main transcriptc.648-11020A>G intron_variant ENST00000340635.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE4DENST00000340635.11 linkuse as main transcriptc.648-11020A>G intron_variant 1 NM_001104631.2 Q08499-1

Frequencies

GnomAD3 genomes
AF:
0.343
AC:
52094
AN:
151926
Hom.:
9258
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.371
Gnomad AMI
AF:
0.348
Gnomad AMR
AF:
0.266
Gnomad ASJ
AF:
0.334
Gnomad EAS
AF:
0.518
Gnomad SAS
AF:
0.546
Gnomad FIN
AF:
0.346
Gnomad MID
AF:
0.320
Gnomad NFE
AF:
0.316
Gnomad OTH
AF:
0.323
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.343
AC:
52164
AN:
152044
Hom.:
9280
Cov.:
32
AF XY:
0.345
AC XY:
25635
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.372
Gnomad4 AMR
AF:
0.266
Gnomad4 ASJ
AF:
0.334
Gnomad4 EAS
AF:
0.518
Gnomad4 SAS
AF:
0.546
Gnomad4 FIN
AF:
0.346
Gnomad4 NFE
AF:
0.316
Gnomad4 OTH
AF:
0.328
Alfa
AF:
0.322
Hom.:
16354
Bravo
AF:
0.333
Asia WGS
AF:
0.553
AC:
1924
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
8.5
DANN
Benign
0.61

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: rs27727; hg19: chr5-58500382; API