rs1549870

Variant names:

• chr2-182252877-G-A
• rs1549870
• NM_001363871.4:c.167+11424C>T

Variant summary

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

The NM_001363871.4(PDE1A):​c.167+11424C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,238 control chromosomes in the GnomAD database, including 1,143 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 0.10 (1143 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.167+11424C>T		intron_variant	Intron 2 of 14	ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.167+11424C>T		intron_variant	Intron 2 of 14	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15658 AN: 152120 Hom.: 1137 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.103 AC: 15668 AN: 152238 Hom.: 1143 Cov.: 32 AF XY: 0.107 AC XY: 7956 AN XY: 74430

African (AFR) AF: 0.0270 AC: 1121 AN: 41564

American (AMR) AF: 0.0815 AC: 1248 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1607 AN: 5160

South Asian (SAS) AF: 0.151 AC: 731 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1907 AN: 10600

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8289 AN: 67996

Other (OTH) AF: 0.113 AC: 238 AN: 2112

Alfa AF: 0.106 Hom.: 579

Bravo AF: 0.0933

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		0.010
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: rs1549870; hg19: chr2-183117604;