dbSNP rs11947234: PDE5A:p.Tyr414Tyr (chr4-119553704-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001083.4(PDE5A):c.1242T>C(p.Tyr414Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,587,744 control chromosomes in the GnomAD database, including 63,140 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 ( 5389 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57751 hom. )

Consequence

PDE5A
NM_001083.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

18 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=1.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4 link	c.1242T>C	p.Tyr414Tyr	synonymous_variant	Exon 8 of 21	ENST00000354960.8	NP_001074.2	O76074-1
PDE5A	NM_033430.3 link	c.1116T>C	p.Tyr372Tyr	synonymous_variant	Exon 8 of 21		NP_236914.2	O76074-2
PDE5A	NM_033437.4 link	c.1086T>C	p.Tyr362Tyr	synonymous_variant	Exon 8 of 21		NP_246273.2	O76074G5E9C5
PDE5A	XM_017008791.3 link	c.1242T>C	p.Tyr414Tyr	synonymous_variant	Exon 8 of 15		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8 link	c.1242T>C	p.Tyr414Tyr	synonymous_variant	Exon 8 of 21	1	NM_001083.4	ENSP00000347046.3		O76074-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39925

AN:

151836

Hom.:

5387

Cov.:

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:

0.380

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.268

AC:

66820

AN:

249726

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.279

AC:

400876

AN:

1435790

Hom.:

57751

Cov.:

AF XY:

0.275

AC XY:

197017

AN XY:

715700

show subpopulations

African (AFR)

AF:

0.199

AC:

6560

AN:

32972

American (AMR)

AF:

0.285

AC:

12607

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5379

AN:

25946

East Asian (EAS)

AF:

0.346

AC:

13600

AN:

39342

South Asian (SAS)

AF:

0.165

AC:

14145

AN:

85658

European-Finnish (FIN)

AF:

0.257

AC:

13716

AN:

53354

Middle Eastern (MID)

AF:

0.187

AC:

1071

AN:

5720

European-Non Finnish (NFE)

AF:

0.292

AC:

317930

AN:

1088922

Other (OTH)

AF:

0.266

AC:

15868

AN:

59570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

12558

25116

37674

50232

62790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10418

20836

31254

41672

52090

<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:

0.263

AC:

39957

AN:

151954

Hom.:

5389

Cov.:

AF XY:

0.261

AC XY:

19378

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.209

AC:

8685

AN:

41490

American (AMR)

AF:

0.265

AC:

4045

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

692

AN:

3464

East Asian (EAS)

AF:

0.380

AC:

1962

AN:

5164

South Asian (SAS)

AF:

0.176

AC:

851

AN:

4824

European-Finnish (FIN)

AF:

0.261

AC:

2752

AN:

10562

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19972

AN:

67876

Other (OTH)

AF:

0.278

AC:

586

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1492

2984

4476

5968

7460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.279

Hom.:

4764

Bravo

AF:

0.267

Asia WGS

AF:

0.248

AC:

860

AN:

3476

EpiCase

AF:

0.288

EpiControl

AF:

0.289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.5

(source)

DANN

Benign

0.89

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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