NM_001083.4:c.831+2415G>A

Variant names:

• chr4-119594108-C-T
• rs2389866
• NM_001083.4:c.831+2415G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083.4(PDE5A):​c.831+2415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,046 control chromosomes in the GnomAD database, including 45,872 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 0.78 (45872 hom., cov: 31)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.831+2415G>A		intron_variant	Intron 3 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.705+2415G>A		intron_variant	Intron 3 of 20		NP_236914.2
PDE5A	NM_033437.4	c.675+2415G>A		intron_variant	Intron 3 of 20		NP_246273.2
PDE5A	XM_017008791.3	c.831+2415G>A		intron_variant	Intron 3 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.831+2415G>A		intron_variant	Intron 3 of 20	1	NM_001083.4	ENSP00000347046.3
PDE5A	ENST00000264805.9	c.705+2415G>A		intron_variant	Intron 3 of 20	1		ENSP00000264805.5
PDE5A	ENST00000394439.5	c.675+2415G>A		intron_variant	Intron 3 of 20	5		ENSP00000377957.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117810 AN: 151928 Hom.: 45836 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.787

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.775 AC: 117901 AN: 152046 Hom.: 45872 Cov.: 31 AF XY: 0.776 AC XY: 57686 AN XY: 74316

African (AFR) AF: 0.720 AC: 29855 AN: 41456

American (AMR) AF: 0.837 AC: 12791 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4612 AN: 5172

South Asian (SAS) AF: 0.811 AC: 3908 AN: 4816

European-Finnish (FIN) AF: 0.727 AC: 7673 AN: 10552

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53391 AN: 67984

Other (OTH) AF: 0.786 AC: 1657 AN: 2108

Alfa AF: 0.776 Hom.: 5907

Bravo AF: 0.781

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.84
DANN	Benign	0.53
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2389866; hg19: chr4-120515263;