12-54551281-G-T

Variant names:

• chr12-54551281-G-T
• rs1022232
• NM_000924.4:c.113+1296G>T

Variant summary

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

The NM_000924.4(PDE1B):​c.113+1296G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,086 control chromosomes in the GnomAD database, including 50,649 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 0.81 (50649 hom., cov: 31)
• Consequence: PDE1B NM_000924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 8 publications found

Genes affected

PDE1B (HGNC:8775): (phosphodiesterase 1B) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE1 subfamily. Members of the PDE1 family are calmodulin-dependent PDEs that are stimulated by a calcium-calmodulin complex. This PDE has dual-specificity for the second messengers, cAMP and cGMP, with a preference for cGMP as a substrate. cAMP and cGMP function as key regulators of many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000924.4. 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
	PDE1B	NM_000924.4	MANE Select	c.113+1296G>T		intron	N/A	NP_000915.1	Q01064-1
	PDE1B	NM_001288769.2		c.-11+1076G>T		intron	N/A	NP_001275698.1	B4DK72
	PDE1B	NM_001288768.2		c.-361+1296G>T		intron	N/A	NP_001275697.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1B	ENST00000243052.8	TSL:1 MANE Select	c.113+1296G>T		intron	N/A	ENSP00000243052.3	Q01064-1
	PDE1B	ENST00000548855.5	TSL:1	n.275+1296G>T		intron	N/A
	PDE1B	ENST00000857306.1		c.113+1296G>T		intron	N/A	ENSP00000527365.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123481 AN: 151968 Hom.: 50607 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.813 AC: 123576 AN: 152086 Hom.: 50649 Cov.: 31 AF XY: 0.813 AC XY: 60438 AN XY: 74342

African (AFR) AF: 0.708 AC: 29331 AN: 41436

American (AMR) AF: 0.803 AC: 12269 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3691 AN: 5170

South Asian (SAS) AF: 0.873 AC: 4203 AN: 4814

European-Finnish (FIN) AF: 0.887 AC: 9403 AN: 10606

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58892 AN: 67988

Other (OTH) AF: 0.841 AC: 1772 AN: 2108

Alfa AF: 0.847 Hom.: 52270

Bravo AF: 0.796

Asia WGS AF: 0.824 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1022232;

hg19: chr12-54945065;