rs1432534

Variant names:

• chr2-182192719-A-C
• rs1432534
• NM_001363871.4:c.1126-3659T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-182192719-A-C
• chr2-182192719-A-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.1126-3659T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,024 control chromosomes in the GnomAD database, including 41,292 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 0.73 (41292 hom., cov: 31)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.1126-3659T>G		intron_variant	Intron 10 of 14	ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.1126-3659T>G		intron_variant	Intron 10 of 14	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111556 AN: 151906 Hom.: 41246 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.734 AC: 111660 AN: 152024 Hom.: 41292 Cov.: 31 AF XY: 0.738 AC XY: 54897 AN XY: 74344

African (AFR) AF: 0.731 AC: 30318 AN: 41466

American (AMR) AF: 0.757 AC: 11553 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4707 AN: 5168

South Asian (SAS) AF: 0.723 AC: 3482 AN: 4818

European-Finnish (FIN) AF: 0.802 AC: 8493 AN: 10594

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48738 AN: 67942

Other (OTH) AF: 0.722 AC: 1521 AN: 2108

Alfa AF: 0.668 Hom.: 2217

Bravo AF: 0.732

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
DANN	Benign	0.66
PhyloP100		-0.73
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: rs1432534; hg19: chr2-183057446;