chr4-119542701-A-C

Variant names:

• chr4-119542701-A-C
• rs2622497
• NM_001083.4:c.1397-67T>G

Variant summary

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

The NM_001083.4(PDE5A):​c.1397-67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,388,026 control chromosomes in the GnomAD database, including 686,326 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 0.97 (72119 hom., cov: 31)
  • Exomes 𝑓: 1.0 (614207 hom.)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1397-67T>G		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1271-67T>G		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1241-67T>G		intron	N/A	NP_246273.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.1397-67T>G		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1271-67T>G		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.251-7678A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.973 AC: 147913 AN: 152054 Hom.: 72074 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.976

GnomAD4 exome AF: 0.997 AC: 1231979 AN: 1235854 Hom.: 614207 AF XY: 0.997 AC XY: 617496 AN XY: 619182

African (AFR) AF: 0.904 AC: 26406 AN: 29196

American (AMR) AF: 0.994 AC: 42155 AN: 42394

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 22795 AN: 22802

East Asian (EAS) AF: 1.00 AC: 38352 AN: 38352

South Asian (SAS) AF: 1.00 AC: 75746 AN: 75764

European-Finnish (FIN) AF: 1.00 AC: 51696 AN: 51700

Middle Eastern (MID) AF: 0.992 AC: 5214 AN: 5254

European-Non Finnish (NFE) AF: 1.00 AC: 917372 AN: 917776

Other (OTH) AF: 0.993 AC: 52243 AN: 52616

GnomAD4 genome AF: 0.973 AC: 148016 AN: 152172 Hom.: 72119 Cov.: 31 AF XY: 0.974 AC XY: 72446 AN XY: 74394

African (AFR) AF: 0.906 AC: 37598 AN: 41486

American (AMR) AF: 0.988 AC: 15102 AN: 15282

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4820 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10597 AN: 10598

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67985 AN: 68020

Other (OTH) AF: 0.976 AC: 2061 AN: 2112

Alfa AF: 0.990 Hom.: 27729

Bravo AF: 0.969

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.29
PhyloP100		-0.63
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: rs2622497; hg19: chr4-120463856;