rs1480936

Variant names:

• chr4-119541706-C-T
• rs1480936
• NM_001083.4:c.1572+753G>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.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
• Publications: 5 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]

ENSG00000291203 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1572+753G>A		intron_variant	Intron 10 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1446+753G>A		intron_variant	Intron 10 of 20		NP_236914.2
PDE5A	NM_033437.4	c.1416+753G>A		intron_variant	Intron 10 of 20		NP_246273.2
PDE5A	XM_017008791.3	c.1572+753G>A		intron_variant	Intron 10 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1572+753G>A		intron_variant	Intron 10 of 20	1	NM_001083.4	ENSP00000347046.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.210 AC: 8690 AN: 41458

American (AMR) AF: 0.265 AC: 4055 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1957 AN: 5160

South Asian (SAS) AF: 0.176 AC: 849 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2767 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20005 AN: 67982

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.265 Hom.: 898

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
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1480936; hg19: chr4-120462861;