rs11975235

chr7-32149928-A-Cchr7-32149928-A-Gchr7-32149928-A-T

Variant summary

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

The NM_001191058.4(PDE1C):c.308+19857T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,028 control chromosomes in the GnomAD database, including 13,585 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 0.42 (13585 hom., cov: 32)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191058.4	c.308+19857T>G		intron_variant
PDE1C	NM_001322058.2	c.308+19857T>G		intron_variant
PDE1C	NM_001322059.2	c.533+19857T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396193.5	c.308+19857T>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63311 AN: 151910 Hom.: 13583 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.417 AC: 63333 AN: 152028 Hom.: 13585 Cov.: 32 AF XY: 0.419 AC XY: 31110 AN XY: 74326

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.442

Alfa AF: 0.375 Hom.: 2371

Bravo AF: 0.414

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	7.0
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11975235; hg19: chr7-32189540;