NM_001363871.4:c.1207+48G>C

Variant names:

• chr2-182188931-C-G
• rs3769796
• NM_001363871.4:c.1207+48G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363871.4(PDE1A):​c.1207+48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,260,056 control chromosomes in the GnomAD database, including 22,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2865 hom., cov: 33)
  • Exomes 𝑓: 0.18 (19643 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.366
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-182188931-C-G is Benign according to our data. Variant chr2-182188931-C-G is described in ClinVar as Benign. ClinVar VariationId is 1291679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 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.1207+48G>C		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1267+48G>C		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1255+48G>C		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.1207+48G>C		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1255+48G>C		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1255+48G>C		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28567 AN: 151970 Hom.: 2857 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.185 AC: 44145 AN: 238244 AF XY: 0.187

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0864

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.183 AC: 203043 AN: 1107968 Hom.: 19643 Cov.: 14 AF XY: 0.183 AC XY: 103982 AN XY: 567136

African (AFR) AF: 0.198 AC: 5161 AN: 26118

American (AMR) AF: 0.0897 AC: 3692 AN: 41148

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2605 AN: 23538

East Asian (EAS) AF: 0.288 AC: 10780 AN: 37426

South Asian (SAS) AF: 0.193 AC: 14694 AN: 76290

European-Finnish (FIN) AF: 0.235 AC: 12467 AN: 52942

Middle Eastern (MID) AF: 0.174 AC: 883 AN: 5066

European-Non Finnish (NFE) AF: 0.180 AC: 143679 AN: 796788

Other (OTH) AF: 0.187 AC: 9082 AN: 48652

GnomAD4 genome AF: 0.188 AC: 28600 AN: 152088 Hom.: 2865 Cov.: 33 AF XY: 0.191 AC XY: 14193 AN XY: 74350

African (AFR) AF: 0.199 AC: 8241 AN: 41498

American (AMR) AF: 0.128 AC: 1959 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1607 AN: 5148

South Asian (SAS) AF: 0.192 AC: 923 AN: 4818

European-Finnish (FIN) AF: 0.240 AC: 2537 AN: 10562

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12357 AN: 67992

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.119 Hom.: 265

Bravo AF: 0.181

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.53
PhyloP100		-0.37
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: rs3769796; hg19: chr2-183053658;