chr4-119550493-A-G

Position:

• chr4-119550493-A-G

Variant summary

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

The NM_001083.4(PDE5A):​c.1396+2057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,140 control chromosomes in the GnomAD database, including 5,642 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 (5636 hom., cov: 32)
  • Exomes 𝑓: 0.31 (6 hom.)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1396+2057T>C		intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1270+2057T>C		intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.1240+2057T>C		intron_variant			NP_246273.2
PDE5A	XM_017008791.3	c.1396+2057T>C		intron_variant			XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1396+2057T>C		intron_variant		1	NM_001083.4	ENSP00000347046
	ENST00000688315.1	n.1390+50A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41160 AN: 151950 Hom.: 5634 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.306 AC: 22 AN: 72 Hom.: 6 Cov.: 0 AF XY: 0.340 AC XY: 17 AN XY: 50

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.271 AC: 41195 AN: 152068 Hom.: 5636 Cov.: 32 AF XY: 0.269 AC XY: 19973 AN XY: 74304

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.284

Alfa AF: 0.271 Hom.: 731

Bravo AF: 0.277

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3822194; hg19: chr4-120471648;