rs12534148

Positions:

• chr7-32208699-G-A

Variant summary

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

The NM_001191058.4(PDE1C):​c.136+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,842 control chromosomes in the GnomAD database, including 3,314 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 0.20 (3314 hom., cov: 31)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

PDE1C (HGNC:8776): (phosphodiesterase 1C) This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191058.4	c.136+790C>T		intron_variant
PDE1C	NM_001322058.2	c.136+790C>T		intron_variant
PDE1C	NM_001322059.2	c.361+790C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396193.5	c.136+790C>T		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29960 AN: 151728 Hom.: 3313 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.197 AC: 29966 AN: 151842 Hom.: 3314 Cov.: 31 AF XY: 0.195 AC XY: 14463 AN XY: 74222

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.195

Alfa AF: 0.236 Hom.: 5769

Bravo AF: 0.195

Asia WGS AF: 0.176 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.085
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12534148; hg19: chr7-32248311;