rs560936

Variant names:

• chr1-66209076-G-T
• rs560936
• NM_002600.4:c.282-38384G>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.282-38384G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,194 control chromosomes in the GnomAD database, including 1,347 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 (1347 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-38384G>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.282-38384G>T		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17943 AN: 152076 Hom.: 1347 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.118 AC: 17938 AN: 152194 Hom.: 1347 Cov.: 32 AF XY: 0.118 AC XY: 8791 AN XY: 74390

African (AFR) AF: 0.0296 AC: 1230 AN: 41550

American (AMR) AF: 0.105 AC: 1610 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3472

East Asian (EAS) AF: 0.138 AC: 716 AN: 5184

South Asian (SAS) AF: 0.0432 AC: 208 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10568

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11281 AN: 68000

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.128 Hom.: 247

Bravo AF: 0.110

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.38
PhyloP100		-0.017
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: rs560936; hg19: chr1-66674759;