Genetic Variant PDE4C:c.*466T>C (chr19-18210463-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098818.4(PDE4C):c.*466T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,724 control chromosomes in the GnomAD database, including 33,225 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 0.65 ( 33083 hom., cov: 33)

Exomes 𝑓: 0.67 ( 142 hom. )

Consequence

PDE4C
NM_001098818.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

13 publications found

Variant links:

Genes affected

PDE4C (HGNC:8782): (phosphodiesterase 4C) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

PDE4C links:

PDE4C (HGNC:):

PDE4C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4C	NM_001098818.4 link	c.*466T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000262805.17	NP_001092288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4C	ENST00000262805.17 link	c.*466T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_001098818.4	ENSP00000262805.10
PDE4C	ENST00000355502.7 link	c.*466T>C		3_prime_UTR_variant	Exon 19 of 19	2		ENSP00000347689.2

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99339

AN:

152000

Hom.:

33055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.654

GnomAD4 exome

AF:

0.668

AC:

405

AN:

606

Hom.:

142

Cov.:

AF XY:

0.690

AC XY:

232

AN XY:

336

show subpopulations

African (AFR)

AF:

0.357

AC:

AN:

American (AMR)

AF:

0.571

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.889

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.675

AC:

289

AN:

428

Other (OTH)

AF:

0.571

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.654

AC:

99420

AN:

152118

Hom.:

33083

Cov.:

AF XY:

0.657

AC XY:

48890

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.528

AC:

21890

AN:

41474

American (AMR)

AF:

0.675

AC:

10312

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2308

AN:

3470

East Asian (EAS)

AF:

0.688

AC:

3560

AN:

5178

South Asian (SAS)

AF:

0.555

AC:

2677

AN:

4822

European-Finnish (FIN)

AF:

0.817

AC:

8647

AN:

10588

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.703

AC:

47784

AN:

67998

Other (OTH)

AF:

0.657

AC:

1385

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1746

3492

5239

6985

8731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.684

Hom.:

46399

Bravo

AF:

0.641

Asia WGS

AF:

0.633

AC:

2204

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.79

(source)

DANN

Benign

0.34

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over