rs3775843

Variant names:

• chr4-119506689-T-C
• rs3775843
• NM_001083.4:c.2190-757A>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.2190-757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,748 control chromosomes in the GnomAD database, including 5,359 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 0.26 (5359 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 6 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	NM_001083.4	MANE Select	c.2190-757A>G		intron	N/A	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.2064-757A>G		intron	N/A	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.2034-757A>G		intron	N/A	NP_246273.2	G5E9C5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.2190-757A>G		intron	N/A	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.2064-757A>G		intron	N/A	ENSP00000264805.5	O76074-2
	PDE5A	ENST00000925607.1		c.2187-757A>G		intron	N/A	ENSP00000595666.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39814 AN: 151632 Hom.: 5357 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.263 AC: 39845 AN: 151748 Hom.: 5359 Cov.: 32 AF XY: 0.261 AC XY: 19316 AN XY: 74144

African (AFR) AF: 0.209 AC: 8658 AN: 41442

American (AMR) AF: 0.265 AC: 4030 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3464

East Asian (EAS) AF: 0.379 AC: 1962 AN: 5172

South Asian (SAS) AF: 0.176 AC: 849 AN: 4826

European-Finnish (FIN) AF: 0.260 AC: 2749 AN: 10556

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19907 AN: 67788

Other (OTH) AF: 0.279 AC: 586 AN: 2100

Alfa AF: 0.265 Hom.: 733

Bravo AF: 0.267

Asia WGS AF: 0.247 AC: 854 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.91
PhyloP100		1.0
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: rs3775843; hg19: chr4-120427844;