Variant chr7-31815964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001191057.4(PDE1C):c.1773C>T(p.Asn591=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 1,613,948 control chromosomes in the GnomAD database, including 770,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71502 hom., cov: 32)

Exomes 𝑓: 0.98 ( 698934 hom. )

Consequence

PDE1C
NM_001191057.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.118

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-31815964-G-A is Benign according to our data. Variant chr7-31815964-G-A is described in ClinVar as [Benign]. Clinvar id is 1233118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.974 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.1773C>T	p.Asn591=	synonymous_variant	15/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6 linkuse as main transcript	c.1773C>T	p.Asn591=	synonymous_variant	15/18	2	NM_001191057.4	A1	Q14123-1

Frequencies

GnomAD3 genomes

AF:

0.969

AC:

147420

AN:

152140

Hom.:

71449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.946

Gnomad AMI

AF:

0.976

Gnomad AMR

AF:

0.980

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.932

Gnomad SAS

AF:

0.960

Gnomad FIN

AF:

0.995

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.980

Gnomad OTH

AF:

0.963

GnomAD3 exomes

AF:

0.972

AC:

244324

AN:

251418

Hom.:

118795

AF XY:

0.972

AC XY:

132120

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.943

Gnomad AMR exome

AF:

0.987

Gnomad ASJ exome

AF:

0.966

Gnomad EAS exome

AF:

0.930

Gnomad SAS exome

AF:

0.959

Gnomad FIN exome

AF:

0.993

Gnomad NFE exome

AF:

0.978

Gnomad OTH exome

AF:

0.973

GnomAD4 exome

AF:

0.978

AC:

1429267

AN:

1461690

Hom.:

698934

Cov.:

AF XY:

0.977

AC XY:

710668

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.941

Gnomad4 AMR exome

AF:

0.987

Gnomad4 ASJ exome

AF:

0.966

Gnomad4 EAS exome

AF:

0.925

Gnomad4 SAS exome

AF:

0.961

Gnomad4 FIN exome

AF:

0.993

Gnomad4 NFE exome

AF:

0.982

Gnomad4 OTH exome

AF:

0.973

GnomAD4 genome

AF:

0.969

AC:

147532

AN:

152258

Hom.:

71502

Cov.:

AF XY:

0.969

AC XY:

72155

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.946

Gnomad4 AMR

AF:

0.980

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

0.932

Gnomad4 SAS

AF:

0.960

Gnomad4 FIN

AF:

0.995

Gnomad4 NFE

AF:

0.980

Gnomad4 OTH

AF:

0.963

Alfa

AF:

0.977

Hom.:

115528

Bravo

AF:

0.967

Asia WGS

AF:

0.940

AC:

3266

AN:

3476

EpiCase

AF:

0.978

EpiControl

AF:

0.976

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Hearing loss, autosomal dominant 74

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.33

DANN

Benign

0.68

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

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