NM_001083.4:c.153-6282G>A

Variant names:

• chr4-119613579-C-T
• rs6847164
• NM_001083.4:c.153-6282G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	NM_001083.4	MANE Select	c.153-6282G>A		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.27-6282G>A		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.-4-6282G>A		intron	N/A	NP_246273.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.153-6282G>A		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.27-6282G>A		intron	N/A	ENSP00000264805.5
	PDE5A	ENST00000925607.1		c.153-6282G>A		intron	N/A	ENSP00000595666.1

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

African (AFR) AF: 0.755 AC: 31316 AN: 41462

American (AMR) AF: 0.866 AC: 13234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4646 AN: 5160

South Asian (SAS) AF: 0.846 AC: 4078 AN: 4820

European-Finnish (FIN) AF: 0.764 AC: 8086 AN: 10578

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55595 AN: 67960

Other (OTH) AF: 0.827 AC: 1744 AN: 2108

Alfa AF: 0.817 Hom.: 105593

Bravo AF: 0.813

Asia WGS AF: 0.874 AC: 3036 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.76
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6847164; hg19: chr4-120534734;