rs1120303

Positions:

• chr5-59454105-G-T

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-238137C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,084 control chromosomes in the GnomAD database, including 7,596 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 0.25 (7596 hom., cov: 33)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.456-238137C>A		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-238137C>A		intron_variant		1	NM_001104631.2	ENSP00000345502

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37458 AN: 151966 Hom.: 7573 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.247 AC: 37525 AN: 152084 Hom.: 7596 Cov.: 33 AF XY: 0.243 AC XY: 18026 AN XY: 74326

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.213

Alfa AF: 0.195 Hom.: 582

Bravo AF: 0.261

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.44

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: rs1120303; hg19: chr5-58749931; COSMIC: COSV58947866;