chr4-119495717-A-G

Variant names:

• chr4-119495717-A-G
• rs11734241
• NM_001083.4:c.*2884T>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.*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
• Publications: 17 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:):

SEPTIN7P14 (HGNC:44219): (septin 7 pseudogene 14)

ACMG classification

Our verdict: Benign. The variant received -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.

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.*2884T>C		3_prime_UTR	Exon 21 of 21	NP_001074.2
	PDE5A	NM_033430.3		c.*2884T>C		3_prime_UTR	Exon 21 of 21	NP_236914.2
	PDE5A	NM_033437.4		c.*2884T>C		3_prime_UTR	Exon 21 of 21	NP_246273.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.*2884T>C		3_prime_UTR	Exon 21 of 21	ENSP00000347046.3
	PDE5A	ENST00000925607.1		c.*2884T>C		3_prime_UTR	Exon 21 of 21	ENSP00000595666.1
	PDE5A	ENST00000925608.1		c.*2884T>C		3_prime_UTR	Exon 20 of 20	ENSP00000595667.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.204 AC: 47 AN: 230

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.227 AC: 9421 AN: 41508

American (AMR) AF: 0.264 AC: 4023 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1977 AN: 5154

South Asian (SAS) AF: 0.176 AC: 852 AN: 4828

European-Finnish (FIN) AF: 0.254 AC: 2692 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19898 AN: 67976

Other (OTH) AF: 0.278 AC: 589 AN: 2116

Alfa AF: 0.275 Hom.: 7603

Bravo AF: 0.271

Asia WGS AF: 0.250 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-0.42
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: rs11734241; hg19: chr4-120416872;