rs11611208

chr12-20605679-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000921.5(PDE3A):c.1012-7764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 152,216 control chromosomes in the GnomAD database, including 146 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 0.039 (146 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

Genes affected

PDE3A (HGNC:8778): (phosphodiesterase 3A) This gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.1012-7764G>A		intron_variant		ENST00000359062.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.1012-7764G>A		intron_variant		1	NM_000921.5	P1
PDE3A	ENST00000544307.1	n.309-7764G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5962 AN: 152098 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0392 AC: 5962 AN: 152216 Hom.: 146 Cov.: 32 AF XY: 0.0376 AC XY: 2801 AN XY: 74418

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0389

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0545

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0527 Hom.: 483

Bravo AF: 0.0375

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.25
Dann	Benign	0.27

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: rs11611208; hg19: chr12-20758613;