Variant 1-66247621-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002600.4(PDE4B):c.443C>T(p.Ala148Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000094 in 1,596,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

PDE4B
NM_002600.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25741696).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	4/17	ENST00000341517.9	NP_002591.2	Q07343-1X5DNX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDE4B	ENST00000341517.9 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	4/17	1	NM_002600.4	ENSP00000342637.4	Q07343-1
PDE4B	ENST00000329654.8 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	4/17	1		ENSP00000332116.4	Q07343-1
PDE4B	ENST00000423207.6 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	2/15	1		ENSP00000392947.2	Q07343-3
PDE4B	ENST00000412480.6 linkuse as main transcript	c.167C>T	p.Ala56Val	missense_variant	2/6	4		ENSP00000397548.2	E9PMG3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000969

AC:

AN:

1444182

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

718186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000906

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.443C>T (p.A148V) alteration is located in exon 4 (coding exon 3) of the PDE4B gene. This alteration results from a C to T substitution at nucleotide position 443, causing the alanine (A) at amino acid position 148 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;T;.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.9

L;L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.027

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.15

B;B;B;.

Vest4

0.55

MutPred

0.092

Gain of methylation at K147 (P = 0.0347);Gain of methylation at K147 (P = 0.0347);.;.;

MVP

0.44

MPC

0.47

ClinPred

0.91

GERP RS

5.8

Varity_R

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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