4-119616229-A-G

Position:

• chr4-119616229-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083.4(PDE5A):​c.153-8932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,252 control chromosomes in the GnomAD database, including 67,794 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 0.94 (67794 hom., cov: 32)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE5A	NM_001083.4	c.153-8932T>C		intron_variant		ENST00000354960.8
PDE5A	NM_033430.3	c.27-8932T>C		intron_variant
PDE5A	NM_033437.4	c.-4-8932T>C		intron_variant
PDE5A	XM_017008791.3	c.153-8932T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8	c.153-8932T>C		intron_variant		1	NM_001083.4
PDE5A	ENST00000264805.9	c.27-8932T>C		intron_variant		1		P1
PDE5A	ENST00000394439.5	c.-4-8932T>C		intron_variant		5
PDE5A	ENST00000420633.1	c.-4-8932T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143502 AN: 152134 Hom.: 67745 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.943 AC: 143609 AN: 152252 Hom.: 67794 Cov.: 32 AF XY: 0.943 AC XY: 70187 AN XY: 74438

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.950

Alfa AF: 0.956 Hom.: 21447

Bravo AF: 0.943

Asia WGS AF: 0.940 AC: 3270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6534145; hg19: chr4-120537384;