1-66226202-C-T

Variant names:

• chr1-66226202-C-T
• rs952635
• NM_002600.4:c.282-21258C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):​c.282-21258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,050 control chromosomes in the GnomAD database, including 32,923 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 0.65 (32923 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-21258C>T		intron_variant	Intron 3 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-21258C>T		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99099 AN: 151932 Hom.: 32885 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.652 AC: 99192 AN: 152050 Hom.: 32923 Cov.: 32 AF XY: 0.644 AC XY: 47848 AN XY: 74324

African (AFR) AF: 0.676 AC: 28016 AN: 41442

American (AMR) AF: 0.545 AC: 8321 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2142 AN: 5170

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4822

European-Finnish (FIN) AF: 0.660 AC: 6978 AN: 10574

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47120 AN: 67982

Other (OTH) AF: 0.666 AC: 1405 AN: 2110

Alfa AF: 0.670 Hom.: 55223

Bravo AF: 0.646

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.44
DANN	Benign	0.13
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs952635; hg19: chr1-66691885;