rs1321172

chr1-66265030-C-Gchr1-66265030-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):c.585-1008C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,148 control chromosomes in the GnomAD database, including 13,740 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 0.39 (13740 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

Genes affected

PDE4B (HGNC:8781): (phosphodiesterase 4B) This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. The encoded protein regulates the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.585-1008C>G		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.585-1008C>G		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59530 AN: 152030 Hom.: 13736 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.391 AC: 59548 AN: 152148 Hom.: 13740 Cov.: 32 AF XY: 0.389 AC XY: 28957 AN XY: 74390

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.382

Alfa AF: 0.349 Hom.: 1125

Bravo AF: 0.366

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.56

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: rs1321172; hg19: chr1-66730713;