4-119524565-A-C

Variant names:

• chr4-119524565-A-C
• rs3822192
• NM_001083.4:c.1779+984T>G

Variant summary

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

The ENST00000354960.8(PDE5A):​c.1779+984T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,068 control chromosomes in the GnomAD database, including 4,952 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 0.25 (4952 hom., cov: 32)
• Consequence: PDE5A ENST00000354960.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• 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]

ENSG00000291203 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354960.8. 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.1779+984T>G		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1653+984T>G		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1623+984T>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.1779+984T>G		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1653+984T>G		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.201-4175A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37419 AN: 151950 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.246 AC: 37433 AN: 152068 Hom.: 4952 Cov.: 32 AF XY: 0.244 AC XY: 18166 AN XY: 74332

African (AFR) AF: 0.151 AC: 6270 AN: 41520

American (AMR) AF: 0.260 AC: 3966 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1961 AN: 5144

South Asian (SAS) AF: 0.176 AC: 849 AN: 4824

European-Finnish (FIN) AF: 0.259 AC: 2746 AN: 10584

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19973 AN: 67954

Other (OTH) AF: 0.266 AC: 563 AN: 2114

Alfa AF: 0.277 Hom.: 7501

Bravo AF: 0.248

Asia WGS AF: 0.245 AC: 852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.48
PhyloP100		1.7
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: rs3822192; hg19: chr4-120445720;