4-119616229-A-G

Variant summary

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

The NM_001083.4(PDE5A):​c.153-8932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,252 control chromosomes in the GnomAD database, including 67,794 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 0.94 ( 67794 hom., cov: 32)

Consequence

PDE5A
NM_001083.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188
Variant links:
Genes affected
PDE5A (HGNC:8784): (phosphodiesterase 5A) This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

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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 (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE5ANM_001083.4 linkuse as main transcriptc.153-8932T>C intron_variant ENST00000354960.8
PDE5ANM_033430.3 linkuse as main transcriptc.27-8932T>C intron_variant
PDE5ANM_033437.4 linkuse as main transcriptc.-4-8932T>C intron_variant
PDE5AXM_017008791.3 linkuse as main transcriptc.153-8932T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE5AENST00000354960.8 linkuse as main transcriptc.153-8932T>C intron_variant 1 NM_001083.4 O76074-1
PDE5AENST00000264805.9 linkuse as main transcriptc.27-8932T>C intron_variant 1 P1O76074-2
PDE5AENST00000394439.5 linkuse as main transcriptc.-4-8932T>C intron_variant 5
PDE5AENST00000420633.1 linkuse as main transcriptc.-4-8932T>C intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.943
AC:
143502
AN:
152134
Hom.:
67745
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.897
Gnomad AMI
AF:
0.997
Gnomad AMR
AF:
0.965
Gnomad ASJ
AF:
0.976
Gnomad EAS
AF:
0.953
Gnomad SAS
AF:
0.930
Gnomad FIN
AF:
0.938
Gnomad MID
AF:
0.943
Gnomad NFE
AF:
0.965
Gnomad OTH
AF:
0.949
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.943
AC:
143609
AN:
152252
Hom.:
67794
Cov.:
32
AF XY:
0.943
AC XY:
70187
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.897
Gnomad4 AMR
AF:
0.965
Gnomad4 ASJ
AF:
0.976
Gnomad4 EAS
AF:
0.953
Gnomad4 SAS
AF:
0.930
Gnomad4 FIN
AF:
0.938
Gnomad4 NFE
AF:
0.965
Gnomad4 OTH
AF:
0.950
Alfa
AF:
0.956
Hom.:
21447
Bravo
AF:
0.943
Asia WGS
AF:
0.940
AC:
3270
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.6
DANN
Benign
0.27

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: rs6534145; hg19: chr4-120537384; API