7-31815955-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001191057.4(PDE1C):c.1782C>T(p.Ala594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,612,540 control chromosomes in the GnomAD database, including 46,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4217 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41853 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-31815955-G-A is Benign according to our data. Variant chr7-31815955-G-A is described in ClinVar as [Benign]. Clinvar id is 1234874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4	c.1782C>T	p.Ala594=	synonymous_variant	15/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6	c.1782C>T	p.Ala594=	synonymous_variant	15/18	2	NM_001191057.4	A1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35325 AN: 151916 Hom.: 4219 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.231 AC: 58170 AN: 251362 Hom.: 7397 AF XY: 0.240 AC XY: 32571 AN XY: 135854

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.235 AC: 342782 AN: 1460506 Hom.: 41853 Cov.: 31 AF XY: 0.238 AC XY: 173168 AN XY: 726626

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.232 AC: 35335 AN: 152034 Hom.: 4217 Cov.: 32 AF XY: 0.227 AC XY: 16873 AN XY: 74314

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.264

Alfa AF: 0.251 Hom.: 8559

Bravo AF: 0.234

Asia WGS AF: 0.208 AC: 725 AN: 3476

EpiCase AF: 0.266

EpiControl AF: 0.270

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hearing loss, autosomal dominant 74 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.31
Dann	Benign	0.80

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: rs2302450; hg19: chr7-31855569; COSMIC: COSV58507186;