Variant 1-66372393-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002600.4(PDE4B):c.1926C>T(p.Leu642Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,972 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 10 hom., cov: 32)

Exomes 𝑓: 0.010 ( 118 hom. )

Consequence

PDE4B
NM_002600.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.04

Variant links:

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]

PDE4B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-66372393-C-T is Benign according to our data. Variant chr1-66372393-C-T is described in ClinVar as [Benign]. Clinvar id is 708064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.04 with no splicing effect.

BS2

High AC in GnomAd4 at 1272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4 linkuse as main transcript	c.1926C>T	p.Leu642Leu	synonymous_variant	17/17	ENST00000341517.9	NP_002591.2	Q07343-1X5DNX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9 linkuse as main transcript	c.1926C>T	p.Leu642Leu	synonymous_variant	17/17	1	NM_002600.4	ENSP00000342637.4		Q07343-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1271

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00853

AC:

2140

AN:

251018

Hom.:

AF XY:

0.00840

AC XY:

1139

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00866

GnomAD4 exome

AF:

0.0103

AC:

15049

AN:

1461736

Hom.:

118

Cov.:

AF XY:

0.0100

AC XY:

7297

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00803

GnomAD4 genome

AF:

0.00836

AC:

1272

AN:

152236

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

619

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0157

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00686

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00931

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.4

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over