rs3769788

Variant names:

• chr2-182194654-C-T
• rs3769788
• NM_001363871.4:c.1126-5594G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363871.4(PDE1A):​c.1126-5594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 151,866 control chromosomes in the GnomAD database, including 41,829 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41829 hom., cov: 31)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.1126-5594G>A		intron	N/A	NP_001350800.1
	PDE1A	NM_001258312.3		c.1186-5594G>A		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1174-5594G>A		intron	N/A	NP_001382187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1126-5594G>A		intron	N/A	ENSP00000386767.1
	PDE1A	ENST00000435564.6	TSL:1	c.1174-5594G>A		intron	N/A	ENSP00000410309.1
	PDE1A	ENST00000410103.2	TSL:1	c.1174-5594G>A		intron	N/A	ENSP00000387037.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112238 AN: 151748 Hom.: 41779 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.723

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112348 AN: 151866 Hom.: 41829 Cov.: 31 AF XY: 0.744 AC XY: 55197 AN XY: 74218

African (AFR) AF: 0.749 AC: 31008 AN: 41412

American (AMR) AF: 0.761 AC: 11589 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4708 AN: 5170

South Asian (SAS) AF: 0.721 AC: 3478 AN: 4822

European-Finnish (FIN) AF: 0.802 AC: 8454 AN: 10544

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.718 AC: 48736 AN: 67910

Other (OTH) AF: 0.727 AC: 1529 AN: 2104

Alfa AF: 0.723 Hom.: 8658

Bravo AF: 0.738

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		0.36
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3769788; hg19: chr2-183059381;