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GeneBe

1-66372393-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002600.4(PDE4B):c.1926C>T(p.Leu642=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.04 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1271 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE4BNM_002600.4 linkuse as main transcriptc.1926C>T p.Leu642= synonymous_variant 17/17 ENST00000341517.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE4BENST00000341517.9 linkuse as main transcriptc.1926C>T p.Leu642= synonymous_variant 17/171 NM_002600.4 A1Q07343-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00836
AC:
1271
AN:
152118
Hom.:
10
Cov.:
32
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.:
14
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00836
AC:
1272
AN:
152236
Hom.:
10
Cov.:
32
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.:
4
Bravo
AF:
0.00686
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0104
EpiControl
AF:
0.00931

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs79722858; hg19: chr1-66838076; COSMIC: COSV100302927; COSMIC: COSV100302927; API