4-119529269-G-A

Variant names:

• chr4-119529269-G-A
• rs10013305
• NM_001083.4:c.1633-3574C>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.1633-3574C>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 151,956 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: -0.286
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 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.1633-3574C>T		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1507-3574C>T		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1477-3574C>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.1633-3574C>T		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1507-3574C>T		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.250+480G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39932 AN: 151838 Hom.: 5385 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: 0.380

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.261

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: 0.263 AC: 39966 AN: 151956 Hom.: 5388 Cov.: 32 AF XY: 0.261 AC XY: 19386 AN XY: 74260

African (AFR) AF: 0.210 AC: 8690 AN: 41452

American (AMR) AF: 0.265 AC: 4042 AN: 15260

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

East Asian (EAS) AF: 0.381 AC: 1964 AN: 5160

South Asian (SAS) AF: 0.176 AC: 846 AN: 4812

European-Finnish (FIN) AF: 0.261 AC: 2760 AN: 10566

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

European-Non Finnish (NFE) AF: 0.294 AC: 19971 AN: 67924

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.189 Hom.: 488

Bravo AF: 0.267

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.29
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: rs10013305; hg19: chr4-120450424;