rs3736115

Variant names:

• chr4-119567548-G-A
• rs3736115
• NM_001083.4:c.832-404C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-119567548-G-A
• chr4-119567548-G-T

Variant summary

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

The NM_001083.4(PDE5A):​c.832-404C>T 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 151,890 control chromosomes in the GnomAD database, including 5,391 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 (5391 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 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.832-404C>T		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.706-404C>T		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.676-404C>T		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.832-404C>T		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.706-404C>T		intron	N/A	ENSP00000264805.5
	PDE5A	ENST00000394439.5	TSL:5	c.676-404C>T		intron	N/A	ENSP00000377957.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39949 AN: 151772 Hom.: 5388 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.262

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: 39983 AN: 151890 Hom.: 5391 Cov.: 32 AF XY: 0.261 AC XY: 19400 AN XY: 74216

African (AFR) AF: 0.210 AC: 8691 AN: 41446

American (AMR) AF: 0.265 AC: 4045 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3462

East Asian (EAS) AF: 0.380 AC: 1956 AN: 5152

South Asian (SAS) AF: 0.176 AC: 849 AN: 4814

European-Finnish (FIN) AF: 0.262 AC: 2761 AN: 10522

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

European-Non Finnish (NFE) AF: 0.294 AC: 19985 AN: 67936

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.265 Hom.: 882

Bravo AF: 0.267

Asia WGS AF: 0.246 AC: 855 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		0.11
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: rs3736115; hg19: chr4-120488703;