rs4655595

chr1-66093076-A-G

Variant summary

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

The NM_002600.4(PDE4B):c.282-154384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,042 control chromosomes in the GnomAD database, including 1,643 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 0.13 (1643 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.282-154384A>G		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-154384A>G		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19952 AN: 151922 Hom.: 1636 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.131 AC: 19992 AN: 152042 Hom.: 1643 Cov.: 32 AF XY: 0.133 AC XY: 9897 AN XY: 74314

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.150

Alfa AF: 0.108 Hom.: 1808

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	7.0
Dann	Benign	0.61

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: rs4655595; hg19: chr1-66558759; COSMIC: COSV58471043; COSMIC: COSV58471043;