chr4-119506689-T-C

Variant summary

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

The NM_001083.4(PDE5A):​c.2190-757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,748 control chromosomes in the GnomAD database, including 5,359 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 0.26 ( 5359 hom., cov: 32)

Consequence

PDE5A
NM_001083.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03
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=-0.75).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDE5ANM_001083.4 linkuse as main transcriptc.2190-757A>G intron_variant ENST00000354960.8 NP_001074.2
PDE5ANM_033430.3 linkuse as main transcriptc.2064-757A>G intron_variant NP_236914.2
PDE5ANM_033437.4 linkuse as main transcriptc.2034-757A>G intron_variant NP_246273.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDE5AENST00000354960.8 linkuse as main transcriptc.2190-757A>G intron_variant 1 NM_001083.4 ENSP00000347046 O76074-1
ENST00000688315.1 linkuse as main transcriptn.1004-5662T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.263
AC:
39814
AN:
151632
Hom.:
5357
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.209
Gnomad AMI
AF:
0.384
Gnomad AMR
AF:
0.265
Gnomad ASJ
AF:
0.200
Gnomad EAS
AF:
0.379
Gnomad SAS
AF:
0.177
Gnomad FIN
AF:
0.260
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.294
Gnomad OTH
AF:
0.281
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.263
AC:
39845
AN:
151748
Hom.:
5359
Cov.:
32
AF XY:
0.261
AC XY:
19316
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.265
Gnomad4 ASJ
AF:
0.200
Gnomad4 EAS
AF:
0.379
Gnomad4 SAS
AF:
0.176
Gnomad4 FIN
AF:
0.260
Gnomad4 NFE
AF:
0.294
Gnomad4 OTH
AF:
0.279
Alfa
AF:
0.266
Hom.:
710
Bravo
AF:
0.267
Asia WGS
AF:
0.247
AC:
854
AN:
3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.7
DANN
Benign
0.91

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: rs3775843; hg19: chr4-120427844; API