4-119542254-T-C

Variant names:

• chr4-119542254-T-C
• rs1010740
• NM_001083.4:c.1572+205A>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.1572+205A>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 152,050 control chromosomes in the GnomAD database, including 5,389 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 (5389 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	NM_001083.4	MANE Select	c.1572+205A>G		intron	N/A	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.1446+205A>G		intron	N/A	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.1416+205A>G		intron	N/A	NP_246273.2	G5E9C5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.1572+205A>G		intron	N/A	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.1446+205A>G		intron	N/A	ENSP00000264805.5	O76074-2
	ENSG00000291203	ENST00000500559.6	TSL:1	n.251-8125T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39940 AN: 151932 Hom.: 5387 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: 0.378

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.210

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: 39972 AN: 152050 Hom.: 5389 Cov.: 32 AF XY: 0.261 AC XY: 19393 AN XY: 74326

African (AFR) AF: 0.209 AC: 8685 AN: 41504

American (AMR) AF: 0.265 AC: 4042 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1945 AN: 5142

South Asian (SAS) AF: 0.176 AC: 850 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2756 AN: 10570

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19996 AN: 67966

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

Alfa AF: 0.265 Hom.: 971

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.65
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: rs1010740; hg19: chr4-120463409;