rs918592

Positions:

• chr5-60401476-C-T

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-90+86466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,092 control chromosomes in the GnomAD database, including 12,418 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 0.36 (12418 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-90+86466G>A		intron_variant			NP_001159371.1
PDE4D	NM_001349241.2	c.-193+86466G>A		intron_variant			NP_001336170.1
PDE4D	NM_001349243.2	c.-674+86466G>A		intron_variant			NP_001336172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+86466G>A		intron_variant		1		ENSP00000423094
PDE4D	ENST00000509355.5	n.157+86466G>A		intron_variant, non_coding_transcript_variant		1
PDE4D	ENST00000505507.6	c.-213+86466G>A		intron_variant		4		ENSP00000425910

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54664 AN: 151974 Hom.: 12375 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.360 AC: 54753 AN: 152092 Hom.: 12418 Cov.: 32 AF XY: 0.358 AC XY: 26636 AN XY: 74354

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.323

Alfa AF: 0.258 Hom.: 7783

Bravo AF: 0.377

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs918592; hg19: chr5-59697303;