rs783036

Positions:

• chr1-66365687-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002600.4(PDE4B):​c.1305G>A​(p.Glu435Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,603,504 control chromosomes in the GnomAD database, including 198,180 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 (24695 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173485 hom.)
• Consequence: PDE4B NM_002600.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.313 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.1305G>A	p.Glu435Glu	synonymous_variant	13/17	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.1305G>A	p.Glu435Glu	synonymous_variant	13/17	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83731 AN: 151930 Hom.: 24653 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.529

GnomAD3 exomes AF: 0.481 AC: 120240 AN: 249924 Hom.: 30796 AF XY: 0.480 AC XY: 64888 AN XY: 135102

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.541

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.482 AC: 700211 AN: 1451456 Hom.: 173485 Cov.: 31 AF XY: 0.483 AC XY: 348169 AN XY: 721184

Gnomad4 AFR exome AF: 0.777

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.551 AC: 83828 AN: 152048 Hom.: 24695 Cov.: 32 AF XY: 0.548 AC XY: 40687 AN XY: 74292

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.532

Alfa AF: 0.497 Hom.: 31055

Bravo AF: 0.556

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs783036; hg19: chr1-66831370; COSMIC: COSV58467637; COSMIC: COSV58467637;