rs4320761

Variant names:

• chr1-66245285-C-T
• rs4320761
• NM_002600.4:c.282-2175C>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.282-2175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,060 control chromosomes in the GnomAD database, including 4,211 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 0.17 (4211 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-2175C>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.282-2175C>T		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26063 AN: 151942 Hom.: 4193 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.172 AC: 26122 AN: 152060 Hom.: 4211 Cov.: 32 AF XY: 0.172 AC XY: 12789 AN XY: 74320

African (AFR) AF: 0.412 AC: 17056 AN: 41434

American (AMR) AF: 0.141 AC: 2159 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1917 AN: 5174

South Asian (SAS) AF: 0.116 AC: 559 AN: 4802

European-Finnish (FIN) AF: 0.0409 AC: 433 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3366 AN: 67988

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.132 Hom.: 486

Bravo AF: 0.193

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		-0.97
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: rs4320761; hg19: chr1-66710968;