rs13134665

Variant names:

• chr4-119505275-T-C
• rs13134665
• NM_001083.4:c.2267+580A>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.2267+580A>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 151,796 control chromosomes in the GnomAD database, including 5,388 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 (5388 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.2267+580A>G		intron_variant	Intron 17 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.2141+580A>G		intron_variant	Intron 17 of 20		NP_236914.2
PDE5A	NM_033437.4	c.2111+580A>G		intron_variant	Intron 17 of 20		NP_246273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.2267+580A>G		intron_variant	Intron 17 of 20	1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39957 AN: 151680 Hom.: 5387 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.263 AC: 39987 AN: 151796 Hom.: 5388 Cov.: 32 AF XY: 0.262 AC XY: 19408 AN XY: 74182

African (AFR) AF: 0.209 AC: 8685 AN: 41470

American (AMR) AF: 0.265 AC: 4036 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1963 AN: 5138

South Asian (SAS) AF: 0.177 AC: 853 AN: 4822

European-Finnish (FIN) AF: 0.262 AC: 2770 AN: 10592

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

European-Non Finnish (NFE) AF: 0.295 AC: 19989 AN: 67784

Other (OTH) AF: 0.279 AC: 587 AN: 2106

Alfa AF: 0.275 Hom.: 1422

Bravo AF: 0.268

Asia WGS AF: 0.248 AC: 862 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.36
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: rs13134665; hg19: chr4-120426430;