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GeneBe

4-119501236-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001083.4(PDE5A):c.2424G>A(p.Glu808=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,607,706 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 16 hom. )

Consequence

PDE5A
NM_001083.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42
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 -13 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=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-119501236-C-T is Benign according to our data. Variant chr4-119501236-C-T is described in ClinVar as [Benign]. Clinvar id is 786047.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=1.41 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 = 0.00917 (1396/152234) while in subpopulation AFR AF= 0.0319 (1324/41546). AF 95% confidence interval is 0.0304. There are 19 homozygotes in gnomad4. There are 638 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 Homozygotes in GnomAd at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE5ANM_001083.4 linkuse as main transcriptc.2424G>A p.Glu808= synonymous_variant 20/21 ENST00000354960.8
PDE5ANM_033430.3 linkuse as main transcriptc.2298G>A p.Glu766= synonymous_variant 20/21
PDE5ANM_033437.4 linkuse as main transcriptc.2268G>A p.Glu756= synonymous_variant 20/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE5AENST00000354960.8 linkuse as main transcriptc.2424G>A p.Glu808= synonymous_variant 20/211 NM_001083.4 O76074-1
ENST00000688315.1 linkuse as main transcriptn.1003+3333C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00912
AC:
1387
AN:
152116
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0317
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00337
GnomAD3 exomes
AF:
0.00226
AC:
567
AN:
250772
Hom.:
5
AF XY:
0.00162
AC XY:
219
AN XY:
135528
show subpopulations
Gnomad AFR exome
AF:
0.0311
Gnomad AMR exome
AF:
0.00133
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000912
AC:
1327
AN:
1455472
Hom.:
16
Cov.:
27
AF XY:
0.000780
AC XY:
565
AN XY:
724638
show subpopulations
Gnomad4 AFR exome
AF:
0.0334
Gnomad4 AMR exome
AF:
0.00168
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000199
Gnomad4 OTH exome
AF:
0.00180
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00917
AC:
1396
AN:
152234
Hom.:
19
Cov.:
32
AF XY:
0.00857
AC XY:
638
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0319
Gnomad4 AMR
AF:
0.00386
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00333
Alfa
AF:
0.00536
Hom.:
4
Bravo
AF:
0.0111
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 testingInvitaeJun 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
8.4
Dann
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs115920291; hg19: chr4-120422391; API