Variant rs3754929 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363871.4(PDE1A):c.776+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,519,524 control chromosomes in the GnomAD database, including 343,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36109 hom., cov: 32)

Exomes 𝑓: 0.67 ( 307751 hom. )

Consequence

PDE1A
NM_001363871.4 splice_region, intron

Scores

Splicing: ADA: 0.00004992

Clinical Significance

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

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

PDE1A (HGNC:8774): (phosphodiesterase 1A) Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).[supplied by OMIM, Oct 2009]

PDE1A links:

PDE1A (HGNC:):

PDE1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-182223857-G-A is Benign according to our data. Variant chr2-182223857-G-A is described in ClinVar as [Benign]. Clinvar id is 1236025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	NM_001363871.4 linkuse as main transcript	c.776+7C>T		splice_region_variant, intron_variant		ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6 linkuse as main transcript	c.776+7C>T		splice_region_variant, intron_variant		5	NM_001363871.4	ENSP00000386767.1		P54750-6

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104351

AN:

151570

Hom.:

36077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.757

Gnomad EAS

AF:

0.731

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.664

Gnomad OTH

AF:

0.707

GnomAD3 exomes

AF:

0.673

AC:

144380

AN:

214446

Hom.:

49071

AF XY:

0.679

AC XY:

79433

AN XY:

117016

show subpopulations

Gnomad AFR exome

AF:

0.734

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.757

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.756

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.670

GnomAD4 exome

AF:

0.669

AC:

915298

AN:

1367836

Hom.:

307751

Cov.:

AF XY:

0.672

AC XY:

457744

AN XY:

681232

show subpopulations

Gnomad4 AFR exome

AF:

0.741

Gnomad4 AMR exome

AF:

0.650

Gnomad4 ASJ exome

AF:

0.754

Gnomad4 EAS exome

AF:

0.706

Gnomad4 SAS exome

AF:

0.754

Gnomad4 FIN exome

AF:

0.575

Gnomad4 NFE exome

AF:

0.662

Gnomad4 OTH exome

AF:

0.680

GnomAD4 genome

AF:

0.688

AC:

104428

AN:

151688

Hom.:

36109

Cov.:

AF XY:

0.686

AC XY:

50817

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.740

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.757

Gnomad4 EAS

AF:

0.732

Gnomad4 SAS

AF:

0.757

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.664

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.673

Hom.:

43038

Bravo

AF:

0.697

Asia WGS

AF:

0.763

AC:

2651

AN:

3476

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.33

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.0

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