dbSNP rs75820400: PDE4D:c.*4659T>G (chr5-58970005-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001104631.2(PDE4D):c.*4659T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,238 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 294 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PDE4D
NM_001104631.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52

Publications

0 publications found

Variant links:

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D Gene-Disease associations (from GenCC):

acrodysostosis 2 with or without hormone resistance
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
acrodysostosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
acrodysostosis with multiple hormone resistance
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
chromosome 5q12 deletion syndrome
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

PDE4D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-58970005-A-C is Benign according to our data. Variant chr5-58970005-A-C is described in ClinVar as Benign. ClinVar VariationId is 353920.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104631.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE4D	NM_001104631.2	MANE Select	c.*4659T>G	3_prime_UTR	Exon 15 of 15	NP_001098101.1	A0A140VJR0
PDE4D	NM_001165899.2		c.*4659T>G	3_prime_UTR	Exon 17 of 17	NP_001159371.1	Q08499-11
PDE4D	NM_001364599.1		c.*4659T>G	3_prime_UTR	Exon 17 of 17	NP_001351528.1	Q08499-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.*4659T>G		3_prime_UTR	Exon 15 of 15	ENSP00000345502.6	Q08499-1
	PDE4D	ENST00000507116.6	TSL:1	c.*4659T>G		3_prime_UTR	Exon 15 of 15	ENSP00000424852.1	Q08499-6

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5228

AN:

152120

Hom.:

289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0272

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0345

AC:

5258

AN:

152238

Hom.:

294

Cov.:

AF XY:

0.0335

AC XY:

2497

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.119

AC:

4934

AN:

41502

American (AMR)

AF:

0.0125

AC:

191

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68008

Other (OTH)

AF:

0.0269

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

231

461

692

922

1153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0151

Hom.:

Bravo

AF:

0.0389

Asia WGS

AF:

0.00723

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Acrodysostosis 2 with or without hormone resistance (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

(source)

DANN

Benign

0.51

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over