rs11734241

Positions:

• chr4-119495717-A-G
• chr4-119495717-A-T

Variant summary

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

The NM_001083.4(PDE5A):​c.*2884T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,336 control chromosomes in the GnomAD database, including 5,489 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 (5483 hom., cov: 32)
  • Exomes 𝑓: 0.20 (6 hom.)
• Consequence: PDE5A NM_001083.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE5A	NM_001083.4	c.*2884T>C		3_prime_UTR_variant	21/21	ENST00000354960.8
SEPTIN7P14	NR_037630.1	n.923+1194A>G		intron_variant, non_coding_transcript_variant
PDE5A	NM_033430.3	c.*2884T>C		3_prime_UTR_variant	21/21
PDE5A	NM_033437.4	c.*2884T>C		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8	c.*2884T>C		3_prime_UTR_variant	21/21	1	NM_001083.4
	ENST00000688315.1	n.910+1194A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40392 AN: 151986 Hom.: 5479 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.203 AC: 47 AN: 232 Hom.: 6 Cov.: 0 AF XY: 0.180 AC XY: 27 AN XY: 150

Gnomad4 FIN exome AF: 0.204

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.266 AC: 40425 AN: 152104 Hom.: 5483 Cov.: 32 AF XY: 0.264 AC XY: 19605 AN XY: 74348

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.278

Alfa AF: 0.274 Hom.: 5738

Bravo AF: 0.271

Asia WGS AF: 0.250 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.58

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: rs11734241; hg19: chr4-120416872;