rs472952

chr1-66335081-A-Gchr1-66335081-A-T

Variant summary

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

The NM_002600.4(PDE4B):c.747+2461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,094 control chromosomes in the GnomAD database, including 23,857 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 0.55 (23857 hom., cov: 33)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.747+2461A>G		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.747+2461A>G		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83644 AN: 151976 Hom.: 23853 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.550 AC: 83688 AN: 152094 Hom.: 23857 Cov.: 33 AF XY: 0.552 AC XY: 41006 AN XY: 74344

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.570

Alfa AF: 0.543 Hom.: 4381

Bravo AF: 0.547

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.56
Dann	Benign	0.45

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: rs472952; hg19: chr1-66800764;