chr4-119495290-C-T

Variant names:

• chr4-119495290-C-T
• rs13124532
• NM_001083.4:c.*3311G>A

Variant summary

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

The NM_001083.4(PDE5A):​c.*3311G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,052 control chromosomes in the GnomAD database, including 1,003 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 0.10 (1003 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE5A NM_001083.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 10 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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.*3311G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.*3311G>A		3_prime_UTR_variant	Exon 21 of 21		NP_236914.2
PDE5A	NM_033437.4	c.*3311G>A		3_prime_UTR_variant	Exon 21 of 21		NP_246273.2
SEPTIN7P14	NR_037630.1	n.923+767C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.*3311G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_001083.4	ENSP00000347046.3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15509 AN: 151934 Hom.: 1007 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0729

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.100

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.102 AC: 15496 AN: 152052 Hom.: 1003 Cov.: 32 AF XY: 0.101 AC XY: 7480 AN XY: 74310

African (AFR) AF: 0.0263 AC: 1093 AN: 41514

American (AMR) AF: 0.0838 AC: 1277 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.0727 AC: 374 AN: 5144

South Asian (SAS) AF: 0.0819 AC: 395 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10556

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9958 AN: 67986

Other (OTH) AF: 0.0991 AC: 209 AN: 2110

Alfa AF: 0.125 Hom.: 3471

Bravo AF: 0.0920

Asia WGS AF: 0.0610 AC: 211 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.9
DANN	Benign	0.89
PhyloP100		-0.067
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: rs13124532; hg19: chr4-120416445;