4-119513249-T-A

Variant names:

• chr4-119513249-T-A
• rs1383532
• NM_001083.4:c.2001-2115A>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.2001-2115A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,972 control chromosomes in the GnomAD database, including 5,368 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 (5368 hom., cov: 31)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.2001-2115A>T		intron_variant	Intron 14 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1875-2115A>T		intron_variant	Intron 14 of 20		NP_236914.2
PDE5A	NM_033437.4	c.1845-2115A>T		intron_variant	Intron 14 of 20		NP_246273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.2001-2115A>T		intron_variant	Intron 14 of 20	1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39836 AN: 151854 Hom.: 5365 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.262 AC: 39870 AN: 151972 Hom.: 5368 Cov.: 31 AF XY: 0.260 AC XY: 19344 AN XY: 74268

African (AFR) AF: 0.208 AC: 8619 AN: 41482

American (AMR) AF: 0.264 AC: 4033 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 691 AN: 3462

East Asian (EAS) AF: 0.380 AC: 1949 AN: 5134

South Asian (SAS) AF: 0.176 AC: 845 AN: 4808

European-Finnish (FIN) AF: 0.260 AC: 2752 AN: 10566

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

European-Non Finnish (NFE) AF: 0.294 AC: 19981 AN: 67960

Other (OTH) AF: 0.279 AC: 586 AN: 2104

Alfa AF: 0.156 Hom.: 300

Bravo AF: 0.267

Asia WGS AF: 0.249 AC: 864 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.53
PhyloP100		-2.2
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: rs1383532; hg19: chr4-120434404;