NM_001083.4:c.1242T>C

Variant names:

• chr4-119553704-A-G
• rs11947234
• NM_001083.4:c.1242T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001083.4(PDE5A):​c.1242T>C​(p.Tyr414Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,587,744 control chromosomes in the GnomAD database, including 63,140 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 0.26 (5389 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57751 hom.)
• Consequence: PDE5A NM_001083.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 18 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:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 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.1242T>C	p.Tyr414Tyr	synonymous	Exon 8 of 21	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.1116T>C	p.Tyr372Tyr	synonymous	Exon 8 of 21	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.1086T>C	p.Tyr362Tyr	synonymous	Exon 8 of 21	NP_246273.2	G5E9C5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.1242T>C	p.Tyr414Tyr	synonymous	Exon 8 of 21	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.1116T>C	p.Tyr372Tyr	synonymous	Exon 8 of 21	ENSP00000264805.5	O76074-2
	PDE5A	ENST00000925607.1		c.1242T>C	p.Tyr414Tyr	synonymous	Exon 8 of 21	ENSP00000595666.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39925 AN: 151836 Hom.: 5387 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.268 AC: 66820 AN: 249726 AF XY: 0.261

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.386

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.279 AC: 400876 AN: 1435790 Hom.: 57751 Cov.: 27 AF XY: 0.275 AC XY: 197017 AN XY: 715700

African (AFR) AF: 0.199 AC: 6560 AN: 32972

American (AMR) AF: 0.285 AC: 12607 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5379 AN: 25946

East Asian (EAS) AF: 0.346 AC: 13600 AN: 39342

South Asian (SAS) AF: 0.165 AC: 14145 AN: 85658

European-Finnish (FIN) AF: 0.257 AC: 13716 AN: 53354

Middle Eastern (MID) AF: 0.187 AC: 1071 AN: 5720

European-Non Finnish (NFE) AF: 0.292 AC: 317930 AN: 1088922

Other (OTH) AF: 0.266 AC: 15868 AN: 59570

GnomAD4 genome AF: 0.263 AC: 39957 AN: 151954 Hom.: 5389 Cov.: 32 AF XY: 0.261 AC XY: 19378 AN XY: 74286

African (AFR) AF: 0.209 AC: 8685 AN: 41490

American (AMR) AF: 0.265 AC: 4045 AN: 15264

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

East Asian (EAS) AF: 0.380 AC: 1962 AN: 5164

South Asian (SAS) AF: 0.176 AC: 851 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2752 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19972 AN: 67876

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.279 Hom.: 4764

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 860 AN: 3476

EpiCase AF: 0.288

EpiControl AF: 0.289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.5
DANN	Benign	0.89
PhyloP100		1.9
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: rs11947234; hg19: chr4-120474859; COSMIC: COSV53345964; COSMIC: COSV53345964;