4-119581306-T-C

Variant names:

• chr4-119581306-T-C
• rs12646525
• NM_001083.4:c.832-14162A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083.4(PDE5A):​c.832-14162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,118 control chromosomes in the GnomAD database, including 44,092 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 0.76 (44092 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 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.832-14162A>G		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.706-14162A>G		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.676-14162A>G		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.832-14162A>G		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.706-14162A>G		intron	N/A	ENSP00000264805.5
	PDE5A	ENST00000394439.5	TSL:5	c.676-14162A>G		intron	N/A	ENSP00000377957.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115275 AN: 152000 Hom.: 44056 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.758 AC: 115363 AN: 152118 Hom.: 44092 Cov.: 32 AF XY: 0.760 AC XY: 56510 AN XY: 74368

African (AFR) AF: 0.662 AC: 27451 AN: 41478

American (AMR) AF: 0.830 AC: 12695 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3032 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4617 AN: 5178

South Asian (SAS) AF: 0.813 AC: 3926 AN: 4828

European-Finnish (FIN) AF: 0.727 AC: 7680 AN: 10566

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53349 AN: 67990

Other (OTH) AF: 0.772 AC: 1633 AN: 2114

Alfa AF: 0.785 Hom.: 132887

Bravo AF: 0.763

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.72
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: rs12646525; hg19: chr4-120502461;