rs12510138

Variant names:

• chr4-119502780-G-C
• rs12510138
• NM_001083.4:c.2332-125C>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.2332-125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 624,998 control chromosomes in the GnomAD database, including 22,835 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 (5493 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17342 hom.)
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 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.2332-125C>G		intron	N/A	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.2206-125C>G		intron	N/A	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.2176-125C>G		intron	N/A	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.2332-125C>G		intron	N/A	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.2206-125C>G		intron	N/A	ENSP00000264805.5	O76074-2
	PDE5A	ENST00000925607.1		c.2329-125C>G		intron	N/A	ENSP00000595666.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40436 AN: 152012 Hom.: 5489 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.267 AC: 126024 AN: 472870 Hom.: 17342 AF XY: 0.260 AC XY: 66666 AN XY: 256114

African (AFR) AF: 0.226 AC: 2898 AN: 12838

American (AMR) AF: 0.282 AC: 5157 AN: 18312

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 2770 AN: 13956

East Asian (EAS) AF: 0.339 AC: 10660 AN: 31486

South Asian (SAS) AF: 0.165 AC: 7677 AN: 46522

European-Finnish (FIN) AF: 0.246 AC: 7969 AN: 32412

Middle Eastern (MID) AF: 0.168 AC: 520 AN: 3100

European-Non Finnish (NFE) AF: 0.283 AC: 81456 AN: 287816

Other (OTH) AF: 0.262 AC: 6917 AN: 26428

GnomAD4 genome AF: 0.266 AC: 40469 AN: 152128 Hom.: 5493 Cov.: 32 AF XY: 0.264 AC XY: 19628 AN XY: 74366

African (AFR) AF: 0.227 AC: 9426 AN: 41516

American (AMR) AF: 0.264 AC: 4039 AN: 15290

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

East Asian (EAS) AF: 0.383 AC: 1976 AN: 5156

South Asian (SAS) AF: 0.176 AC: 850 AN: 4828

European-Finnish (FIN) AF: 0.254 AC: 2691 AN: 10588

Middle Eastern (MID) AF: 0.212 AC: 61 AN: 288

European-Non Finnish (NFE) AF: 0.293 AC: 19927 AN: 67966

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

Alfa AF: 0.268 Hom.: 718

Bravo AF: 0.271

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12510138; hg19: chr4-120423935;