rs702543

Positions:

• chr5-59546948-C-T

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-330980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,948 control chromosomes in the GnomAD database, including 18,500 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 0.45 (18500 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.456-330980G>A		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-330980G>A		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68273 AN: 151830 Hom.: 18504 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.449 AC: 68267 AN: 151948 Hom.: 18500 Cov.: 32 AF XY: 0.451 AC XY: 33499 AN XY: 74254

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.488

Alfa AF: 0.567 Hom.: 54101

Bravo AF: 0.436

Asia WGS AF: 0.621 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs702543; hg19: chr5-58842774;