1-66166947-G-A

Position:

• chr1-66166947-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.282-80513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,130 control chromosomes in the GnomAD database, including 43,338 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 0.75 (43338 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.282-80513G>A		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-80513G>A		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114116 AN: 152012 Hom.: 43276 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.751 AC: 114237 AN: 152130 Hom.: 43338 Cov.: 32 AF XY: 0.754 AC XY: 56102 AN XY: 74364

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.738

Alfa AF: 0.730 Hom.: 6893

Bravo AF: 0.751

Asia WGS AF: 0.852 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.34

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: rs536025; hg19: chr1-66632630;