rs2503222

Variant names:

• chr1-66053014-C-T
• rs2503222
• NM_002600.4:c.281+134179C>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.281+134179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,050 control chromosomes in the GnomAD database, including 1,267 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 0.12 (1267 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 6 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 = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.281+134179C>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.281+134179C>T		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18142 AN: 151934 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.120 AC: 18182 AN: 152050 Hom.: 1267 Cov.: 32 AF XY: 0.122 AC XY: 9083 AN XY: 74312

African (AFR) AF: 0.145 AC: 6020 AN: 41472

American (AMR) AF: 0.193 AC: 2950 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4828

European-Finnish (FIN) AF: 0.0936 AC: 989 AN: 10562

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5764 AN: 67972

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.103 Hom.: 517

Bravo AF: 0.126

Asia WGS AF: 0.189 AC: 657 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.68
PhyloP100		-0.39
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: rs2503222; hg19: chr1-66518697; COSMIC: COSV58470948; COSMIC: COSV58470948;