rs599235

Variant names:

• chr1-66160690-G-A
• rs599235
• NM_002600.4:c.282-86770G>A

Variant summary

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

The ENST00000341517.9(PDE4B):​c.282-86770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,076 control chromosomes in the GnomAD database, including 5,193 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 0.25 (5193 hom., cov: 33)
• Consequence: PDE4B ENST00000341517.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341517.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.282-86770G>A		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.282-86770G>A		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.237-86770G>A		intron	N/A	NP_001032417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.282-86770G>A		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.282-86770G>A		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.237-86770G>A		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37947 AN: 151958 Hom.: 5193 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.249 AC: 37943 AN: 152076 Hom.: 5193 Cov.: 33 AF XY: 0.246 AC XY: 18289 AN XY: 74328

African (AFR) AF: 0.143 AC: 5949 AN: 41494

American (AMR) AF: 0.295 AC: 4509 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3470

East Asian (EAS) AF: 0.113 AC: 587 AN: 5182

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2660 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21208 AN: 67964

Other (OTH) AF: 0.261 AC: 552 AN: 2114

Alfa AF: 0.260 Hom.: 720

Bravo AF: 0.249

Asia WGS AF: 0.147 AC: 512 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-0.46
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: rs599235; hg19: chr1-66626373;