rs10066510

chr5-59938731-C-A

Variant summary

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

The ENST00000502484.6(PDE4D):c.272+49757G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,104 control chromosomes in the GnomAD database, including 3,029 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 0.16 (3029 hom., cov: 33)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.272+49757G>T		intron_variant
PDE4D	NM_001349241.2	c.242+49757G>T		intron_variant
PDE4D	NM_001349243.2	c.-240+49757G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.272+49757G>T		intron_variant		1
PDE4D	ENST00000512069.6	n.217+49757G>T		intron_variant, non_coding_transcript_variant		2
PDE4D	ENST00000514231.1	n.145+49757G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24374 AN: 151986 Hom.: 3025 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.160 AC: 24381 AN: 152104 Hom.: 3029 Cov.: 33 AF XY: 0.153 AC XY: 11392 AN XY: 74364

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.0855

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.167

Alfa AF: 0.123 Hom.: 813

Bravo AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10066510; hg19: chr5-59234558;