rs1354064

chr1-66038036-A-Cchr1-66038036-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):c.281+119201A>C 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 150,702 control chromosomes in the GnomAD database, including 1,210 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 (1210 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.281+119201A>C		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.281+119201A>C		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17763 AN: 150582 Hom.: 1205 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.118 AC: 17804 AN: 150702 Hom.: 1210 Cov.: 32 AF XY: 0.120 AC XY: 8861 AN XY: 73770

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0860 Hom.: 350

Bravo AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.19
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1354064; hg19: chr1-66503719; COSMIC: COSV58470939; COSMIC: COSV58470939;