rs1480936

Positions:

• chr4-119541706-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.1572+753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,046 control chromosomes in the GnomAD database, including 5,401 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 0.26 (5401 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1572+753G>A		intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1446+753G>A		intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.1416+753G>A		intron_variant			NP_246273.2
PDE5A	XM_017008791.3	c.1572+753G>A		intron_variant			XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1572+753G>A		intron_variant		1	NM_001083.4	ENSP00000347046
	ENST00000688315.1	n.1326-8673C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39983 AN: 151928 Hom.: 5398 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.281

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.263 AC: 40017 AN: 152046 Hom.: 5401 Cov.: 32 AF XY: 0.261 AC XY: 19420 AN XY: 74312

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.280

Alfa AF: 0.266 Hom.: 879

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1480936; hg19: chr4-120462861;