rs2503177

Variant names:

• chr1-66146821-G-A
• rs2503177
• NM_002600.4:c.282-100639G>A

Variant summary

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

The NM_002600.4(PDE4B):​c.282-100639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,148 control chromosomes in the GnomAD database, including 48,401 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 0.79 (48401 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-100639G>A		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.282-100639G>A		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120821 AN: 152030 Hom.: 48365 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.795 AC: 120911 AN: 152148 Hom.: 48401 Cov.: 32 AF XY: 0.790 AC XY: 58783 AN XY: 74362

African (AFR) AF: 0.793 AC: 32916 AN: 41512

American (AMR) AF: 0.755 AC: 11540 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2998 AN: 5164

South Asian (SAS) AF: 0.601 AC: 2895 AN: 4820

European-Finnish (FIN) AF: 0.816 AC: 8637 AN: 10584

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.830 AC: 56448 AN: 68000

Other (OTH) AF: 0.787 AC: 1658 AN: 2108

Alfa AF: 0.811 Hom.: 25481

Bravo AF: 0.790

Asia WGS AF: 0.577 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		0.17
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: rs2503177; hg19: chr1-66612504;