4-119511122-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001083.4(PDE5A):c.2013A>C(p.Pro671=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,607,088 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (45 hom.)
• Consequence: PDE5A NM_001083.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.69

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-119511122-T-G is Benign according to our data. Variant chr4-119511122-T-G is described in ClinVar as [Benign]. Clinvar id is 789729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.69 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE5A	NM_001083.4	c.2013A>C	p.Pro671=	synonymous_variant	15/21	ENST00000354960.8
PDE5A	NM_033430.3	c.1887A>C	p.Pro629=	synonymous_variant	15/21
PDE5A	NM_033437.4	c.1857A>C	p.Pro619=	synonymous_variant	15/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8	c.2013A>C	p.Pro671=	synonymous_variant	15/21	1	NM_001083.4
	ENST00000688315.1	n.1004-1229T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2283 AN: 152074 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00571

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00410 AC: 1027 AN: 250484 Hom.: 27 AF XY: 0.00290 AC XY: 392 AN XY: 135374

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00163 AC: 2367 AN: 1454896 Hom.: 45 Cov.: 27 AF XY: 0.00140 AC XY: 1014 AN XY: 724100

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000155

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.0150 AC: 2286 AN: 152192 Hom.: 59 Cov.: 32 AF XY: 0.0148 AC XY: 1099 AN XY: 74420

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.00563

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00816 Hom.: 19

Bravo AF: 0.0174

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.090
Dann	Benign	0.65

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: rs61729464; hg19: chr4-120432277;