7-31809092-A-G

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.1830T>C(p.Gly610=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,582,904 control chromosomes in the GnomAD database, including 30,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3092 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27781 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0620

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=-0.51).
• BP6: Variant 7-31809092-A-G is Benign according to our data. Variant chr7-31809092-A-G is described in ClinVar as [Benign]. Clinvar id is 1241492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.062 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4	c.1830T>C	p.Gly610=	synonymous_variant	16/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6	c.1830T>C	p.Gly610=	synonymous_variant	16/18	2	NM_001191057.4	A1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30170 AN: 151776 Hom.: 3093 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.193 AC: 48076 AN: 248792 Hom.: 4947 AF XY: 0.199 AC XY: 26729 AN XY: 134496

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.239

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.193 AC: 275697 AN: 1431010 Hom.: 27781 Cov.: 26 AF XY: 0.195 AC XY: 139424 AN XY: 713878

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.199 AC: 30194 AN: 151894 Hom.: 3092 Cov.: 32 AF XY: 0.195 AC XY: 14468 AN XY: 74240

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.212

Alfa AF: 0.208 Hom.: 5797

Bravo AF: 0.204

Asia WGS AF: 0.157 AC: 545 AN: 3474

EpiCase AF: 0.215

EpiControl AF: 0.221

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	-0.51
Cadd	Benign	6.2
Dann	Benign	0.76

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: rs3213709; hg19: chr7-31848706; COSMIC: COSV58507169;