rs3769789

Variant names:

• chr2-182194473-T-C
• rs3769789
• NM_001363871.4:c.1126-5413A>G

Variant summary

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

The NM_001363871.4(PDE1A):​c.1126-5413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,060 control chromosomes in the GnomAD database, including 2,546 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 0.18 (2546 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.1126-5413A>G		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1186-5413A>G		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1174-5413A>G		intron	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1126-5413A>G		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1174-5413A>G		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1174-5413A>G		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26666 AN: 151942 Hom.: 2539 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.176 AC: 26696 AN: 152060 Hom.: 2546 Cov.: 32 AF XY: 0.179 AC XY: 13307 AN XY: 74324

African (AFR) AF: 0.154 AC: 6376 AN: 41514

American (AMR) AF: 0.123 AC: 1876 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1603 AN: 5166

South Asian (SAS) AF: 0.191 AC: 923 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2532 AN: 10576

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12402 AN: 67942

Other (OTH) AF: 0.161 AC: 340 AN: 2106

Alfa AF: 0.174 Hom.: 3800

Bravo AF: 0.167

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs3769789; hg19: chr2-183059200;