rs6847164

Positions:

• chr4-119613579-C-T

Variant summary

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

The NM_001083.4(PDE5A):​c.153-6282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,044 control chromosomes in the GnomAD database, including 49,792 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 0.81 (49792 hom., cov: 31)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 -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 = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.153-6282G>A		intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.27-6282G>A		intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.-4-6282G>A		intron_variant			NP_246273.2
PDE5A	XM_017008791.3	c.153-6282G>A		intron_variant			XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.153-6282G>A		intron_variant		1	NM_001083.4	ENSP00000347046
PDE5A	ENST00000264805.9	c.27-6282G>A		intron_variant		1		ENSP00000264805	P1
PDE5A	ENST00000394439.5	c.-4-6282G>A		intron_variant		5		ENSP00000377957
PDE5A	ENST00000420633.1	c.-4-6282G>A		intron_variant		3		ENSP00000416309

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122765 AN: 151926 Hom.: 49749 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.808 AC: 122858 AN: 152044 Hom.: 49792 Cov.: 31 AF XY: 0.809 AC XY: 60166 AN XY: 74326

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.827

Alfa AF: 0.822 Hom.: 68416

Bravo AF: 0.813

Asia WGS AF: 0.874 AC: 3036 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.76

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: rs6847164; hg19: chr4-120534734;