Variant 4-119542606-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001083.4(PDE5A):c.1425G>A(p.Glu475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,613,854 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 19 hom. )

Consequence

PDE5A
NM_001083.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.196

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]

PDE5A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 4-119542606-C-T is Benign according to our data. Variant chr4-119542606-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.196 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDE5A	NM_001083.4 linkuse as main transcript	c.1425G>A	p.Glu475=	synonymous_variant	10/21	ENST00000354960.8
PDE5A	NM_033430.3 linkuse as main transcript	c.1299G>A	p.Glu433=	synonymous_variant	10/21
PDE5A	NM_033437.4 linkuse as main transcript	c.1269G>A	p.Glu423=	synonymous_variant	10/21
PDE5A	XM_017008791.3 linkuse as main transcript	c.1425G>A	p.Glu475=	synonymous_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8 linkuse as main transcript	c.1425G>A	p.Glu475=	synonymous_variant	10/21	1	NM_001083.4		O76074-1
	ENST00000688315.1 linkuse as main transcript	n.1326-7773C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00222

AC:

557

AN:

251254

Hom.:

AF XY:

0.00225

AC XY:

306

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00914

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00369

AC:

5387

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

2622

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00919

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00199

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00411

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00213

AC:

324

AN:

152226

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00329

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00221

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00338

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 16, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	PDE5A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

6.6

DANN

Benign

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over