rs4503327

Variant names:

• chr1-65941124-T-C
• rs4503327
• NM_002600.4:c.281+22289T>C

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+22289T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,824 control chromosomes in the GnomAD database, including 8,953 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 0.34 (8953 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.281+22289T>C		intron_variant	Intron 3 of 16	ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.281+22289T>C		intron_variant	Intron 3 of 16		NP_001032418.1
PDE4B	NM_001297441.1	c.46+27764T>C		intron_variant	Intron 1 of 15		NP_001284370.1
PDE4B	NM_001297440.2	c.5+27768T>C		intron_variant	Intron 2 of 15		NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.281+22289T>C		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.281+22289T>C		intron_variant	Intron 3 of 16	1		ENSP00000332116.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51138 AN: 151706 Hom.: 8943 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.337 AC: 51182 AN: 151824 Hom.: 8953 Cov.: 31 AF XY: 0.338 AC XY: 25097 AN XY: 74188

African (AFR) AF: 0.248 AC: 10266 AN: 41476

American (AMR) AF: 0.394 AC: 6001 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1420 AN: 3456

East Asian (EAS) AF: 0.485 AC: 2492 AN: 5136

South Asian (SAS) AF: 0.446 AC: 2151 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3157 AN: 10532

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24446 AN: 67878

Other (OTH) AF: 0.360 AC: 755 AN: 2098

Alfa AF: 0.358 Hom.: 5375

Bravo AF: 0.339

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4503327; hg19: chr1-66406807;