dbSNP rs12510138: PDE5A:c.2332-125C>G (chr4-119502780-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001083.4(PDE5A):c.2332-125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 624,998 control chromosomes in the GnomAD database, including 22,835 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 0.27 ( 5493 hom., cov: 32)

Exomes 𝑓: 0.27 ( 17342 hom. )

Consequence

PDE5A
NM_001083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

12 publications found

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:

ENSG00000291203 (HGNC:):

ENSG00000291203 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4 link	c.2332-125C>G	intron_variant	Intron 18 of 20	ENST00000354960.8	NP_001074.2	O76074-1
PDE5A	NM_033430.3 link	c.2206-125C>G	intron_variant	Intron 18 of 20		NP_236914.2	O76074-2
PDE5A	NM_033437.4 link	c.2176-125C>G	intron_variant	Intron 18 of 20		NP_246273.2	O76074G5E9C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8 link	c.2332-125C>G		intron_variant	Intron 18 of 20	1	NM_001083.4	ENSP00000347046.3		O76074-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40436

AN:

152012

Hom.:

5489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.208

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.267

AC:

126024

AN:

472870

Hom.:

17342

AF XY:

0.260

AC XY:

66666

AN XY:

256114

show subpopulations

African (AFR)

AF:

0.226

AC:

2898

AN:

12838

American (AMR)

AF:

0.282

AC:

5157

AN:

18312

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

2770

AN:

13956

East Asian (EAS)

AF:

0.339

AC:

10660

AN:

31486

South Asian (SAS)

AF:

0.165

AC:

7677

AN:

46522

European-Finnish (FIN)

AF:

0.246

AC:

7969

AN:

32412

Middle Eastern (MID)

AF:

0.168

AC:

520

AN:

3100

European-Non Finnish (NFE)

AF:

0.283

AC:

81456

AN:

287816

Other (OTH)

AF:

0.262

AC:

6917

AN:

26428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

4058

8115

12173

16230

20288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.266

AC:

40469

AN:

152128

Hom.:

5493

Cov.:

AF XY:

0.264

AC XY:

19628

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.227

AC:

9426

AN:

41516

American (AMR)

AF:

0.264

AC:

4039

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

658

AN:

3470

East Asian (EAS)

AF:

0.383

AC:

1976

AN:

5156

South Asian (SAS)

AF:

0.176

AC:

850

AN:

4828

European-Finnish (FIN)

AF:

0.254

AC:

2691

AN:

10588

Middle Eastern (MID)

AF:

0.212

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.293

AC:

19927

AN:

67966

Other (OTH)

AF:

0.278

AC:

589

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1513

3027

4540

6054

7567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.268

Hom.:

718

Bravo

AF:

0.271

Asia WGS

AF:

0.250

AC:

869

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

2.3

(source)

DANN

Benign

0.50

PhyloP100

0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over