rs1480940

Variant names:

• chr4-119536527-T-C
• rs1480940
• NM_001083.4:c.1632+2433A>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.1632+2433A>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 152,080 control chromosomes in the GnomAD database, including 5,396 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 (5396 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 5 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=-0.94).
• 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.1632+2433A>G		intron_variant	Intron 11 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1506+2433A>G		intron_variant	Intron 11 of 20		NP_236914.2
PDE5A	NM_033437.4	c.1476+2433A>G		intron_variant	Intron 11 of 20		NP_246273.2
PDE5A	XM_017008791.3	c.1632+2433A>G		intron_variant	Intron 11 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1632+2433A>G		intron_variant	Intron 11 of 20	1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39976 AN: 151962 Hom.: 5393 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.207

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: 40010 AN: 152080 Hom.: 5396 Cov.: 32 AF XY: 0.261 AC XY: 19419 AN XY: 74328

African (AFR) AF: 0.209 AC: 8696 AN: 41518

American (AMR) AF: 0.265 AC: 4042 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1965 AN: 5168

South Asian (SAS) AF: 0.176 AC: 849 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2771 AN: 10596

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19990 AN: 67922

Other (OTH) AF: 0.280 AC: 591 AN: 2114

Alfa AF: 0.267 Hom.: 879

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.75
DANN	Benign	0.51
PhyloP100		-0.97
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: rs1480940; hg19: chr4-120457682;