rs215738

Positions:

• chr7-32404823-G-A
• chr7-32404823-G-C
• chr7-32404823-G-T

Variant summary

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

The NM_001322059.2(PDE1C):​c.310+22999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,176 control chromosomes in the GnomAD database, including 57,139 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 0.85 (57139 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001322059.2	c.310+22999C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000672256.1	c.310+22999C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129118 AN: 152058 Hom.: 57135 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.849 AC: 129164 AN: 152176 Hom.: 57139 Cov.: 32 AF XY: 0.850 AC XY: 63263 AN XY: 74404

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.862

Alfa AF: 0.949 Hom.: 133683

Bravo AF: 0.833

Asia WGS AF: 0.879 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs215738; hg19: chr7-32444435;