rs7528545

chr1-66227081-T-C

Variant summary

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

The NM_002600.4(PDE4B):c.282-20379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,106 control chromosomes in the GnomAD database, including 29,306 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 0.61 (29306 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.282-20379T>C		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-20379T>C		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93332 AN: 151988 Hom.: 29277 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.614 AC: 93409 AN: 152106 Hom.: 29306 Cov.: 32 AF XY: 0.606 AC XY: 45076 AN XY: 74358

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.640

Alfa AF: 0.646 Hom.: 5959

Bravo AF: 0.603

Asia WGS AF: 0.415 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
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: rs7528545; hg19: chr1-66692764;