Genetic Variant NM_001083.4:c.*2884T>C (chr4-119495717-A-G) – 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.*2884T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,336 control chromosomes in the GnomAD database, including 5,489 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 ( 5483 hom., cov: 32)

Exomes 𝑓: 0.20 ( 6 hom. )

Consequence

PDE5A
NM_001083.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.420

Publications

17 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:

SEPTIN7P14 (HGNC:44219): (septin 7 pseudogene 14)

SEPTIN7P14 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4 link	c.*2884T>C	3_prime_UTR_variant	Exon 21 of 21	ENST00000354960.8	NP_001074.2	O76074-1
PDE5A	NM_033430.3 link	c.*2884T>C	3_prime_UTR_variant	Exon 21 of 21		NP_236914.2	O76074-2
PDE5A	NM_033437.4 link	c.*2884T>C	3_prime_UTR_variant	Exon 21 of 21		NP_246273.2	O76074G5E9C5
SEPTIN7P14	NR_037630.1 link	n.923+1194A>G	intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8 link	c.*2884T>C		3_prime_UTR_variant	Exon 21 of 21	1	NM_001083.4	ENSP00000347046.3		O76074-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40392

AN:

151986

Hom.:

5479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.203

AC:

AN:

232

Hom.:

Cov.:

AF XY:

0.180

AC XY:

AN XY:

150

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.204

AC:

AN:

230

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.266

AC:

40425

AN:

152104

Hom.:

5483

Cov.:

AF XY:

0.264

AC XY:

19605

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.227

AC:

9421

AN:

41508

American (AMR)

AF:

0.264

AC:

4023

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

658

AN:

3470

East Asian (EAS)

AF:

0.384

AC:

1977

AN:

5154

South Asian (SAS)

AF:

0.176

AC:

852

AN:

4828

European-Finnish (FIN)

AF:

0.254

AC:

2692

AN:

10588

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19898

AN:

67976

Other (OTH)

AF:

0.278

AC:

589

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1528

3055

4583

6110

7638

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:

0.275

Hom.:

7603

Bravo

AF:

0.271

Asia WGS

AF:

0.250

AC:

870

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

(source)

DANN

Benign

0.58

PhyloP100

-0.42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over