rs12510138

Variant names:

• chr4-119502780-G-C
• rs12510138
• NM_001083.4:c.2332-125C>G

Variant summary

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

The NM_001083.4(PDE5A):​c.2332-125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 624,998 control chromosomes in the GnomAD database, including 22,835 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 0.27 (5493 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17342 hom.)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.2332-125C>G		intron_variant	Intron 18 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.2206-125C>G		intron_variant	Intron 18 of 20		NP_236914.2
PDE5A	NM_033437.4	c.2176-125C>G		intron_variant	Intron 18 of 20		NP_246273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.2332-125C>G		intron_variant	Intron 18 of 20	1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40436 AN: 152012 Hom.: 5489 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.267 AC: 126024 AN: 472870 Hom.: 17342 AF XY: 0.260 AC XY: 66666 AN XY: 256114

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.266 AC: 40469 AN: 152128 Hom.: 5493 Cov.: 32 AF XY: 0.264 AC XY: 19628 AN XY: 74366

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.278

Alfa AF: 0.268 Hom.: 718

Bravo AF: 0.271

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12510138; hg19: chr4-120423935;