Genetic Variant NM_001083.4:c.1396+2057T>C (chr4-119550493-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.1396+2057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,140 control chromosomes in the GnomAD database, including 5,642 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 ( 5636 hom., cov: 32)

Exomes 𝑓: 0.31 ( 6 hom. )

Consequence

PDE5A
NM_001083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

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:

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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=-0.91).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE5A	NM_001083.4	MANE Select	c.1396+2057T>C	intron	N/A	NP_001074.2	O76074-1
PDE5A	NM_033430.3		c.1270+2057T>C	intron	N/A	NP_236914.2	O76074-2
PDE5A	NM_033437.4		c.1240+2057T>C	intron	N/A	NP_246273.2	G5E9C5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.1396+2057T>C	intron	N/A	ENSP00000347046.3	O76074-1
PDE5A	ENST00000264805.9	TSL:1	c.1270+2057T>C	intron	N/A	ENSP00000264805.5	O76074-2
ENSG00000291203	ENST00000500559.6	TSL:1	n.315+50A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41160

AN:

151950

Hom.:

5634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.268

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:

0.286

GnomAD4 exome

AF:

0.306

AC:

AN:

Hom.:

Cov.:

AF XY:

0.340

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.188

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.364

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.271

AC:

41195

AN:

152068

Hom.:

5636

Cov.:

AF XY:

0.269

AC XY:

19973

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.236

AC:

9798

AN:

41472

American (AMR)

AF:

0.269

AC:

4104

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

693

AN:

3472

East Asian (EAS)

AF:

0.381

AC:

1960

AN:

5144

South Asian (SAS)

AF:

0.176

AC:

848

AN:

4816

European-Finnish (FIN)

AF:

0.261

AC:

2765

AN:

10592

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

20014

AN:

67984

Other (OTH)

AF:

0.284

AC:

599

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1561

3122

4682

6243

7804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.269

Hom.:

755

Bravo

AF:

0.277

Asia WGS

AF:

0.248

AC:

862

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.043

(source)

DANN

Benign

0.17

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over