12-54551281-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1B	NM_000924.4	c.113+1296G>T		intron_variant	Intron 2 of 15	ENST00000243052.8	NP_000915.1
PDE1B	NM_001288769.2	c.-11+1076G>T		intron_variant	Intron 1 of 14		NP_001275698.1
PDE1B	NM_001288768.2	c.-361+1296G>T		intron_variant	Intron 2 of 15		NP_001275697.1
PDE1B	XM_047428970.1	c.-46+1296G>T		intron_variant	Intron 1 of 15		XP_047284926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1B	ENST00000243052.8	c.113+1296G>T		intron_variant	Intron 2 of 15	1	NM_000924.4	ENSP00000243052.3

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

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.841

Alfa AF: 0.852 Hom.: 33232

Bravo AF: 0.796

Asia WGS AF: 0.824 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1022232; hg19: chr12-54945065;