rs2622497

Positions:

• chr4-119542701-A-C
• chr4-119542701-A-G
• chr4-119542701-A-T

Variant summary

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

The ENST00000354960.8(PDE5A):​c.1397-67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,388,026 control chromosomes in the GnomAD database, including 686,326 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 0.97 (72119 hom., cov: 31)
  • Exomes 𝑓: 1.0 (614207 hom.)
• Consequence: PDE5A ENST00000354960.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1397-67T>G		intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1271-67T>G		intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.1241-67T>G		intron_variant			NP_246273.2
PDE5A	XM_017008791.3	c.1397-67T>G		intron_variant			XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1397-67T>G		intron_variant		1	NM_001083.4	ENSP00000347046
	ENST00000688315.1	n.1326-7678A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.973 AC: 147913 AN: 152054 Hom.: 72074 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.976

GnomAD4 exome AF: 0.997 AC: 1231979 AN: 1235854 Hom.: 614207 AF XY: 0.997 AC XY: 617496 AN XY: 619182

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.994

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.993

GnomAD4 genome AF: 0.973 AC: 148016 AN: 152172 Hom.: 72119 Cov.: 31 AF XY: 0.974 AC XY: 72446 AN XY: 74394

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.976

Alfa AF: 0.990 Hom.: 23563

Bravo AF: 0.969

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.29

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: rs2622497; hg19: chr4-120463856;