4-119537712-T-C

Position:

• chr4-119537712-T-C

Variant summary

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

The NM_001083.4(PDE5A):​c.1632+1248A>G 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 151,414 control chromosomes in the GnomAD database, including 5,350 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 (5350 hom., cov: 30)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.93).
• 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.1632+1248A>G		intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1506+1248A>G		intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.1476+1248A>G		intron_variant			NP_246273.2
PDE5A	XM_017008791.3	c.1632+1248A>G		intron_variant			XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1632+1248A>G		intron_variant		1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39751 AN: 151294 Hom.: 5346 Cov.: 30

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.263 AC: 39787 AN: 151414 Hom.: 5350 Cov.: 30 AF XY: 0.261 AC XY: 19283 AN XY: 73958

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.278

Alfa AF: 0.266 Hom.: 955

Bravo AF: 0.267

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.62

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: rs6835635; hg19: chr4-120458867;