Variant 7-31753535-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001191057.4(PDE1C):c.1979G>A(p.Arg660His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,610,002 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 33 hom. )

Consequence

PDE1C
NM_001191057.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.49

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056877136).

BP6

Variant 7-31753535-C-T is Benign according to our data. Variant chr7-31753535-C-T is described in ClinVar as [Benign]. Clinvar id is 709900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 847 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4 linkuse as main transcript	c.1979G>A	p.Arg660His	missense_variant	18/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6 linkuse as main transcript	c.1979G>A	p.Arg660His	missense_variant	18/18	2	NM_001191057.4	A1	Q14123-1
PDE1C	ENST00000396193.5 linkuse as main transcript	c.2159G>A	p.Arg720His	missense_variant	19/19	2		A1
PDE1C	ENST00000321453.12 linkuse as main transcript	c.1979G>A	p.Arg660His	missense_variant	19/19	2		A1	Q14123-1

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

847

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00590

AC:

1406

AN:

238244

Hom.:

AF XY:

0.00614

AC XY:

803

AN XY:

130788

show subpopulations

Gnomad AFR exome

AF:

0.000635

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00961

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.00175

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00624

AC:

9102

AN:

1457762

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

4576

AN XY:

725052

show subpopulations

Gnomad4 AFR exome

AF:

0.000450

Gnomad4 AMR exome

AF:

0.000902

Gnomad4 ASJ exome

AF:

0.00854

Gnomad4 EAS exome

AF:

0.000531

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.0226

Gnomad4 NFE exome

AF:

0.00647

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.00556

AC:

847

AN:

152240

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.00337

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000571

AC:

ESP6500EA

AF:

0.00552

AC:

ExAC

AF:

0.00561

AC:

652

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00641

EpiControl

AF:

0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	PDE1C: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.87

D;.;D

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.86

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.084

MVP

0.72

MPC

0.033

ClinPred

0.023

GERP RS

4.5

Varity_R

0.045

gMVP

0.27

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