rs10059859

Positions:

• chr5-59935480-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165899.2(PDE4D):​c.272+53008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,042 control chromosomes in the GnomAD database, including 11,399 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 0.27 (11399 hom., cov: 32)
• Consequence: PDE4D NM_001165899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.272+53008G>A		intron_variant			NP_001159371.1
PDE4D	NM_001364599.1	c.272+53008G>A		intron_variant			NP_001351528.1
PDE4D	NM_001349241.2	c.242+53008G>A		intron_variant			NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.272+53008G>A		intron_variant		1		ENSP00000423094.2
PDE4D	ENST00000512069.6	n.217+53008G>A		intron_variant		2
PDE4D	ENST00000514231.1	n.145+53008G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40603 AN: 151926 Hom.: 11348 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40704 AN: 152042 Hom.: 11399 Cov.: 32 AF XY: 0.258 AC XY: 19193 AN XY: 74330

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.250

Alfa AF: 0.126 Hom.: 3081

Bravo AF: 0.298

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10059859; hg19: chr5-59231307;