Genetic Variant NM_001083.4:c.1573-132A>G (chr4-119539151-T-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.1573-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 724,076 control chromosomes in the GnomAD database, including 26,903 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 ( 5383 hom., cov: 32)

Exomes 𝑓: 0.27 ( 21520 hom. )

Consequence

PDE5A
NM_001083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

8 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4 link	c.1573-132A>G	intron_variant	Intron 10 of 20	ENST00000354960.8	NP_001074.2	O76074-1
PDE5A	NM_033430.3 link	c.1447-132A>G	intron_variant	Intron 10 of 20		NP_236914.2	O76074-2
PDE5A	NM_033437.4 link	c.1417-132A>G	intron_variant	Intron 10 of 20		NP_246273.2	O76074G5E9C5
PDE5A	XM_017008791.3 link	c.1573-132A>G	intron_variant	Intron 10 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8 link	c.1573-132A>G		intron_variant	Intron 10 of 20	1	NM_001083.4	ENSP00000347046.3		O76074-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39932

AN:

151866

Hom.:

5381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.270

AC:

154253

AN:

572092

Hom.:

21520

AF XY:

0.264

AC XY:

80863

AN XY:

306698

show subpopulations

African (AFR)

AF:

0.206

AC:

3091

AN:

15006

American (AMR)

AF:

0.283

AC:

8230

AN:

29048

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

3473

AN:

16932

East Asian (EAS)

AF:

0.346

AC:

11983

AN:

34644

South Asian (SAS)

AF:

0.165

AC:

9238

AN:

56124

European-Finnish (FIN)

AF:

0.257

AC:

12637

AN:

49230

Middle Eastern (MID)

AF:

0.178

AC:

658

AN:

3700

European-Non Finnish (NFE)

AF:

0.288

AC:

97105

AN:

337692

Other (OTH)

AF:

0.264

AC:

7838

AN:

29716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5276

10552

15829

21105

26381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1068

2136

3204

4272

5340

<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:

39964

AN:

151984

Hom.:

5383

Cov.:

AF XY:

0.261

AC XY:

19398

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.209

AC:

8677

AN:

41482

American (AMR)

AF:

0.265

AC:

4035

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

693

AN:

3470

East Asian (EAS)

AF:

0.381

AC:

1963

AN:

5150

South Asian (SAS)

AF:

0.176

AC:

848

AN:

4822

European-Finnish (FIN)

AF:

0.261

AC:

2760

AN:

10572

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19985

AN:

67928

Other (OTH)

AF:

0.280

AC:

591

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1501

3001

4502

6002

7503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.265

Hom.:

983

Bravo

AF:

0.267

Asia WGS

AF:

0.248

AC:

862

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.0

(source)

DANN

Benign

0.42

PhyloP100

0.031

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