rs11947234

Positions:

• chr4-119553704-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000354960.8(PDE5A):​c.1242T>C​(p.Tyr414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,587,744 control chromosomes in the GnomAD database, including 63,140 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 (5389 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57751 hom.)
• Consequence: PDE5A ENST00000354960.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1242T>C	p.Tyr414=	synonymous_variant	8/21	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1116T>C	p.Tyr372=	synonymous_variant	8/21		NP_236914.2
PDE5A	NM_033437.4	c.1086T>C	p.Tyr362=	synonymous_variant	8/21		NP_246273.2
PDE5A	XM_017008791.3	c.1242T>C	p.Tyr414=	synonymous_variant	8/15		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1242T>C	p.Tyr414=	synonymous_variant	8/21	1	NM_001083.4	ENSP00000347046
PDE5A	ENST00000264805.9	c.1116T>C	p.Tyr372=	synonymous_variant	8/21	1		ENSP00000264805	P1
PDE5A	ENST00000394439.5	c.1086T>C	p.Tyr362=	synonymous_variant	8/21	5		ENSP00000377957
PDE5A	ENST00000508914.1	n.251T>C		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39925 AN: 151836 Hom.: 5387 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.280

GnomAD3 exomes AF: 0.268 AC: 66820 AN: 249726 Hom.: 9517 AF XY: 0.261 AC XY: 35249 AN XY: 135096

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.386

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.279 AC: 400876 AN: 1435790 Hom.: 57751 Cov.: 27 AF XY: 0.275 AC XY: 197017 AN XY: 715700

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.263 AC: 39957 AN: 151954 Hom.: 5389 Cov.: 32 AF XY: 0.261 AC XY: 19378 AN XY: 74286

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.278

Alfa AF: 0.279 Hom.: 4265

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 860 AN: 3476

EpiCase AF: 0.288

EpiControl AF: 0.289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.5
DANN	Benign	0.89

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: rs11947234; hg19: chr4-120474859; COSMIC: COSV53345964; COSMIC: COSV53345964;