4-119601017-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083.4(PDE5A):c.742-4405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,122 control chromosomes in the GnomAD database, including 3,332 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 0.21 (3332 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE5A	NM_001083.4	c.742-4405G>A		intron_variant		ENST00000354960.8
PDE5A	NM_033430.3	c.616-4405G>A		intron_variant
PDE5A	NM_033437.4	c.586-4405G>A		intron_variant
PDE5A	XM_017008791.3	c.742-4405G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8	c.742-4405G>A		intron_variant		1	NM_001083.4
PDE5A	ENST00000264805.9	c.616-4405G>A		intron_variant		1		P1
PDE5A	ENST00000394439.5	c.586-4405G>A		intron_variant		5
PDE5A	ENST00000420633.1	c.586-4405G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31387 AN: 152004 Hom.: 3328 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.206 AC: 31411 AN: 152122 Hom.: 3332 Cov.: 32 AF XY: 0.206 AC XY: 15309 AN XY: 74342

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.201

Alfa AF: 0.202 Hom.: 4106

Bravo AF: 0.198

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.4
Dann	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs10518335; hg19: chr4-120522172;