rs159195

Positions:

• chr5-59538207-C-A

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-322239G>T 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 152,000 control chromosomes in the GnomAD database, including 4,085 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 (4085 hom., cov: 33)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.456-322239G>T		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-322239G>T		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33706 AN: 151882 Hom.: 4084 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.222 AC: 33730 AN: 152000 Hom.: 4085 Cov.: 33 AF XY: 0.220 AC XY: 16360 AN XY: 74308

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.233

Alfa AF: 0.222 Hom.: 5515

Bravo AF: 0.218

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.72

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: rs159195; hg19: chr5-58834033;