rs599235

chr1-66160690-G-A

Variant summary

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

The NM_002600.4(PDE4B):c.282-86770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,076 control chromosomes in the GnomAD database, including 5,193 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 0.25 (5193 hom., cov: 33)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.282-86770G>A		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-86770G>A		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37947 AN: 151958 Hom.: 5193 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.249 AC: 37943 AN: 152076 Hom.: 5193 Cov.: 33 AF XY: 0.246 AC XY: 18289 AN XY: 74328

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.261

Alfa AF: 0.265 Hom.: 707

Bravo AF: 0.249

Asia WGS AF: 0.147 AC: 512 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.65
Dann	Benign	0.52

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: rs599235; hg19: chr1-66626373;