rs11731756

Variant names:

• chr4-119557541-T-G
• rs11731756
• NM_001083.4:c.1199+2755A>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.1199+2755A>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 151,828 control chromosomes in the GnomAD database, including 5,621 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 (5621 hom., cov: 31)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.1199+2755A>C		intron_variant	Intron 7 of 20	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.1073+2755A>C		intron_variant	Intron 7 of 20		NP_236914.2
PDE5A	NM_033437.4	c.1043+2755A>C		intron_variant	Intron 7 of 20		NP_246273.2
PDE5A	XM_017008791.3	c.1199+2755A>C		intron_variant	Intron 7 of 14		XP_016864280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.1199+2755A>C		intron_variant	Intron 7 of 20	1	NM_001083.4	ENSP00000347046.3
PDE5A	ENST00000264805.9	c.1073+2755A>C		intron_variant	Intron 7 of 20	1		ENSP00000264805.5
PDE5A	ENST00000394439.5	c.1043+2755A>C		intron_variant	Intron 7 of 20	5		ENSP00000377957.1
PDE5A	ENST00000508914.1	n.208+2755A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41093 AN: 151710 Hom.: 5619 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.271 AC: 41128 AN: 151828 Hom.: 5621 Cov.: 31 AF XY: 0.269 AC XY: 19952 AN XY: 74166

African (AFR) AF: 0.237 AC: 9801 AN: 41412

American (AMR) AF: 0.268 AC: 4092 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3464

East Asian (EAS) AF: 0.381 AC: 1959 AN: 5146

South Asian (SAS) AF: 0.177 AC: 850 AN: 4808

European-Finnish (FIN) AF: 0.261 AC: 2747 AN: 10518

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

European-Non Finnish (NFE) AF: 0.294 AC: 19982 AN: 67942

Other (OTH) AF: 0.283 AC: 594 AN: 2096

Alfa AF: 0.269 Hom.: 753

Bravo AF: 0.276

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.4
DANN	Benign	0.83
PhyloP100		-0.36
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: rs11731756; hg19: chr4-120478696;