dbSNP rs2622497: PDE5A:c.1397-67T>G (chr4-119542701-A-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.1397-67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,388,026 control chromosomes in the GnomAD database, including 686,326 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 0.97 ( 72119 hom., cov: 31)

Exomes 𝑓: 1.0 ( 614207 hom. )

Consequence

PDE5A
NM_001083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.625

Publications

5 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4 link	c.1397-67T>G	intron_variant	Intron 9 of 20	ENST00000354960.8	NP_001074.2	O76074-1
PDE5A	NM_033430.3 link	c.1271-67T>G	intron_variant	Intron 9 of 20		NP_236914.2	O76074-2
PDE5A	NM_033437.4 link	c.1241-67T>G	intron_variant	Intron 9 of 20		NP_246273.2	O76074G5E9C5
PDE5A	XM_017008791.3 link	c.1397-67T>G	intron_variant	Intron 9 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8 link	c.1397-67T>G		intron_variant	Intron 9 of 20	1	NM_001083.4	ENSP00000347046.3		O76074-1

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

147913

AN:

152054

Hom.:

72074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.976

GnomAD4 exome

AF:

0.997

AC:

1231979

AN:

1235854

Hom.:

614207

AF XY:

0.997

AC XY:

617496

AN XY:

619182

show subpopulations

African (AFR)

AF:

0.904

AC:

26406

AN:

29196

American (AMR)

AF:

0.994

AC:

42155

AN:

42394

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

22795

AN:

22802

East Asian (EAS)

AF:

1.00

AC:

38352

AN:

38352

South Asian (SAS)

AF:

1.00

AC:

75746

AN:

75764

European-Finnish (FIN)

AF:

1.00

AC:

51696

AN:

51700

Middle Eastern (MID)

AF:

0.992

AC:

5214

AN:

5254

European-Non Finnish (NFE)

AF:

1.00

AC:

917372

AN:

917776

Other (OTH)

AF:

0.993

AC:

52243

AN:

52616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

167

335

502

670

837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16998

33996

50994

67992

84990

<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:

0.973

AC:

148016

AN:

152172

Hom.:

72119

Cov.:

AF XY:

0.974

AC XY:

72446

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.906

AC:

37598

AN:

41486

American (AMR)

AF:

0.988

AC:

15102

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3470

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5178

AN:

5178

South Asian (SAS)

AF:

1.00

AC:

4820

AN:

4820

European-Finnish (FIN)

AF:

1.00

AC:

10597

AN:

10598

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67985

AN:

68020

Other (OTH)

AF:

0.976

AC:

2061

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

193

386

579

772

965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.990

Hom.:

27729

Bravo

AF:

0.969

Asia WGS

AF:

0.995

AC:

3459

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.35

(source)

DANN

Benign

0.29

PhyloP100

-0.63

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