rs6865647

Positions:

• chr5-59103374-A-G
• chr5-59103374-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001104631.2(PDE4D):​c.809-64403T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,100 control chromosomes in the GnomAD database, including 2,813 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 0.18 (2813 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.809-64403T>C		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.809-64403T>C		intron_variant		1	NM_001104631.2	ENSP00000345502

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27202 AN: 151982 Hom.: 2803 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.179 AC: 27239 AN: 152100 Hom.: 2813 Cov.: 32 AF XY: 0.179 AC XY: 13338 AN XY: 74358

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.150

Alfa AF: 0.132 Hom.: 1860

Bravo AF: 0.187

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6865647; hg19: chr5-58399201;