rs1155576

Variant names:

• chr4-119529004-A-C
• rs1155576
• NM_001083.4:c.1633-3309T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-119529004-A-C
• chr4-119529004-A-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.1633-3309T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,960 control chromosomes in the GnomAD database, including 6,578 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 0.29 (6578 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 13 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=-1.01).
• 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.1633-3309T>G		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1507-3309T>G		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1477-3309T>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.1633-3309T>G		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1507-3309T>G		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.250+215A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44540 AN: 151842 Hom.: 6575 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.293 AC: 44581 AN: 151960 Hom.: 6578 Cov.: 32 AF XY: 0.291 AC XY: 21621 AN XY: 74246

African (AFR) AF: 0.314 AC: 13029 AN: 41444

American (AMR) AF: 0.277 AC: 4222 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3462

East Asian (EAS) AF: 0.380 AC: 1948 AN: 5132

South Asian (SAS) AF: 0.176 AC: 848 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2758 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20035 AN: 67940

Other (OTH) AF: 0.298 AC: 631 AN: 2114

Alfa AF: 0.290 Hom.: 20329

Bravo AF: 0.302

Asia WGS AF: 0.254 AC: 883 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		-0.13
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: rs1155576; hg19: chr4-120450159;