4-119601017-C-T

Variant names:

• chr4-119601017-C-T
• rs10518335
• NM_001083.4:c.742-4405G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083.4(PDE5A):​c.742-4405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,122 control chromosomes in the GnomAD database, including 3,332 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 0.21 (3332 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 9 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]

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 (AFR) allele frequency at 95% confidence interval = 0.213 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.742-4405G>A		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.616-4405G>A		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.586-4405G>A		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.742-4405G>A		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.616-4405G>A		intron	N/A	ENSP00000264805.5
	PDE5A	ENST00000394439.5	TSL:5	c.586-4405G>A		intron	N/A	ENSP00000377957.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31387 AN: 152004 Hom.: 3328 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.206 AC: 31411 AN: 152122 Hom.: 3332 Cov.: 32 AF XY: 0.206 AC XY: 15309 AN XY: 74342

African (AFR) AF: 0.217 AC: 9001 AN: 41502

American (AMR) AF: 0.156 AC: 2385 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3466

East Asian (EAS) AF: 0.111 AC: 577 AN: 5180

South Asian (SAS) AF: 0.188 AC: 905 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2879 AN: 10562

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14524 AN: 67998

Other (OTH) AF: 0.201 AC: 425 AN: 2116

Alfa AF: 0.202 Hom.: 5231

Bravo AF: 0.198

Asia WGS AF: 0.153 AC: 532 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	2.4
DANN	Benign	0.52
PhyloP100		-0.039
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: rs10518335; hg19: chr4-120522172;