4-119550493-A-G

Variant names:

• chr4-119550493-A-G
• rs3822194
• NM_001083.4:c.1396+2057T>C

Variant summary

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

The NM_001083.4(PDE5A):​c.1396+2057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,140 control chromosomes in the GnomAD database, including 5,642 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 0.27 (5636 hom., cov: 32)
  • Exomes 𝑓: 0.31 (6 hom.)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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=-0.91).
• 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.1396+2057T>C		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1270+2057T>C		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1240+2057T>C		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.1396+2057T>C		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1270+2057T>C		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.315+50A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41160 AN: 151950 Hom.: 5634 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.306 AC: 22 AN: 72 Hom.: 6 Cov.: 0 AF XY: 0.340 AC XY: 17 AN XY: 50

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.188 AC: 3 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.364 AC: 16 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.271 AC: 41195 AN: 152068 Hom.: 5636 Cov.: 32 AF XY: 0.269 AC XY: 19973 AN XY: 74304

African (AFR) AF: 0.236 AC: 9798 AN: 41472

American (AMR) AF: 0.269 AC: 4104 AN: 15276

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

East Asian (EAS) AF: 0.381 AC: 1960 AN: 5144

South Asian (SAS) AF: 0.176 AC: 848 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2765 AN: 10592

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

European-Non Finnish (NFE) AF: 0.294 AC: 20014 AN: 67984

Other (OTH) AF: 0.284 AC: 599 AN: 2108

Alfa AF: 0.269 Hom.: 755

Bravo AF: 0.277

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.17
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3822194; hg19: chr4-120471648;