rs12404118

Variant names:

• chr1-66107570-G-A
• rs12404118
• NM_002600.4:c.282-139890G>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.282-139890G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 151,356 control chromosomes in the GnomAD database, including 427 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 0.063 (427 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-139890G>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.282-139890G>A		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9453 AN: 151272 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.0626 AC: 9471 AN: 151356 Hom.: 427 Cov.: 32 AF XY: 0.0618 AC XY: 4568 AN XY: 73878

African (AFR) AF: 0.0189 AC: 782 AN: 41386

American (AMR) AF: 0.0781 AC: 1183 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3460

East Asian (EAS) AF: 0.00407 AC: 21 AN: 5156

South Asian (SAS) AF: 0.175 AC: 836 AN: 4784

European-Finnish (FIN) AF: 0.0348 AC: 360 AN: 10334

Middle Eastern (MID) AF: 0.139 AC: 40 AN: 288

European-Non Finnish (NFE) AF: 0.0820 AC: 5560 AN: 67792

Other (OTH) AF: 0.0912 AC: 191 AN: 2094

Alfa AF: 0.0817 Hom.: 411

Bravo AF: 0.0619

Asia WGS AF: 0.101 AC: 350 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.30
PhyloP100		1.2
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: rs12404118; hg19: chr1-66573253; COSMIC: COSV58471101;