dbSNP rs16878206: PDE4D:c.-90+1084T>C (chr5-60520967-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 ENST00000504876.2(PART1):n.218-53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,342 control chromosomes in the GnomAD database, including 15,536 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 0.38 ( 15523 hom., cov: 32)

Exomes 𝑓: 0.24 ( 13 hom. )

Consequence

PART1
ENST00000504876.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

6 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 links:

PART1 (HGNC:17263): (prostate androgen-regulated transcript 1) This gene is induced by androgen in prostate adenocarcinoma cells. Multiple alternatively transcript variants have been described for this gene, none of which are predicted to encode a protein product. [provided by RefSeq, Sep 2009]

PART1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000504876.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504876.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	NR_024617.1		n.712-8437A>G		intron	N/A
	PART1	NR_028509.1		n.493-53A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
PART1	ENST00000504876.2	TSL:2	n.218-53A>G	intron	N/A
PDE4D	ENST00000506510.6	TSL:4	n.70+1084T>C	intron	N/A
PART1	ENST00000506884.2	TSL:2	n.301-8437A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58177

AN:

151922

Hom.:

15469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.0194

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.238

AC:

AN:

302

Hom.:

AF XY:

0.190

AC XY:

AN XY:

210

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.341

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.201

AC:

AN:

194

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.383

AC:

58285

AN:

152040

Hom.:

15523

Cov.:

AF XY:

0.375

AC XY:

27862

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.760

AC:

31487

AN:

41430

American (AMR)

AF:

0.242

AC:

3701

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1088

AN:

3468

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5182

South Asian (SAS)

AF:

0.201

AC:

968

AN:

4812

European-Finnish (FIN)

AF:

0.249

AC:

2626

AN:

10564

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17325

AN:

67978

Other (OTH)

AF:

0.347

AC:

732

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1399

2799

4198

5598

6997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.361

Hom.:

1682

Bravo

AF:

0.397

Asia WGS

AF:

0.150

AC:

524

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.068

(source)

DANN

Benign

0.24

PhyloP100

-1.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over