rs3822192

chr4-119524565-A-Cchr4-119524565-A-T

Variant summary

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

The NM_001083.4(PDE5A):c.1779+984T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,068 control chromosomes in the GnomAD database, including 4,952 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 0.25 (4952 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE5A	NM_001083.4	c.1779+984T>G		intron_variant		ENST00000354960.8
PDE5A	NM_033430.3	c.1653+984T>G		intron_variant
PDE5A	NM_033437.4	c.1623+984T>G		intron_variant
PDE5A	XM_017008791.3	c.1779+984T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8	c.1779+984T>G		intron_variant		1	NM_001083.4
	ENST00000688315.1	n.1276-4175A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37419 AN: 151950 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.246 AC: 37433 AN: 152068 Hom.: 4952 Cov.: 32 AF XY: 0.244 AC XY: 18166 AN XY: 74332

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.266

Alfa AF: 0.282 Hom.: 5778

Bravo AF: 0.248

Asia WGS AF: 0.245 AC: 852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.8
Dann	Benign	0.48

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: rs3822192; hg19: chr4-120445720;