5-59289472-T-C

Position:

• chr5-59289472-T-C

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-73504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,694 control chromosomes in the GnomAD database, including 5,217 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 0.22 (5217 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.456-73504A>G		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-73504A>G		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33660 AN: 151576 Hom.: 5215 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.222 AC: 33695 AN: 151694 Hom.: 5217 Cov.: 32 AF XY: 0.226 AC XY: 16724 AN XY: 74102

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.208

Alfa AF: 0.166 Hom.: 349

Bravo AF: 0.229

Asia WGS AF: 0.449 AC: 1557 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.56

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: rs34738; hg19: chr5-58585298;