Variant 7-31775712-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001191057.4(PDE1C):c.1912G>A(p.Gly638Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,612,688 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 50 hom. )

Consequence

PDE1C
NM_001191057.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.390

Variant links:

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]

PDE1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002098769).

BP6

Variant 7-31775712-C-T is Benign according to our data. Variant chr7-31775712-C-T is described in ClinVar as [Benign]. Clinvar id is 3038497.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4 linkuse as main transcript	c.1912G>A	p.Gly638Ser	missense_variant	17/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6 linkuse as main transcript	c.1912G>A	p.Gly638Ser	missense_variant	17/18	2	NM_001191057.4	A1	Q14123-1
PDE1C	ENST00000396193.5 linkuse as main transcript	c.2092G>A	p.Gly698Ser	missense_variant	18/19	2		A1
PDE1C	ENST00000321453.12 linkuse as main transcript	c.1912G>A	p.Gly638Ser	missense_variant	18/19	2		A1	Q14123-1

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00519

AC:

1253

AN:

241536

Hom.:

AF XY:

0.00475

AC XY:

630

AN XY:

132608

show subpopulations

Gnomad AFR exome

AF:

0.000490

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.0659

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00168

AC:

2447

AN:

1460540

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1185

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0512

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.0000956

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00235

AC:

357

AN:

152148

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000675

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0580

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000439

Hom.:

Bravo

AF:

0.00292

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00515

AC:

604

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PDE1C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.3

DANN

Benign

0.57

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.78

T;.;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.25

.;B;B

Vest4

0.28

MVP

0.38

MPC

0.029

ClinPred

0.0062

GERP RS

2.6

Varity_R

0.033

gMVP

0.24

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over