rs4384209

Positions:

• chr1-65813442-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.-71+20194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 150,730 control chromosomes in the GnomAD database, including 35,627 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 0.68 (35627 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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 = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.-71+20194A>G		intron_variant		ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.-71+20812A>G		intron_variant			NP_001032418.1
PDE4B	NM_001297440.2	c.-108+20812A>G		intron_variant			NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.-71+20194A>G		intron_variant		1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.-71+20812A>G		intron_variant		1		ENSP00000332116.4

Frequencies

GnomAD3 genomes AF: 0.677 AC: 101915 AN: 150632 Hom.: 35630 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.676 AC: 101939 AN: 150730 Hom.: 35627 Cov.: 31 AF XY: 0.672 AC XY: 49515 AN XY: 73654

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.685

Alfa AF: 0.761 Hom.: 70632

Bravo AF: 0.653

Asia WGS AF: 0.482 AC: 1678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4384209; hg19: chr1-66279125;