rs6450530

Positions:

• chr5-59763682-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.455+129486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,972 control chromosomes in the GnomAD database, including 16,836 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 0.46 (16836 hom., cov: 31)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.455+129486A>G		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.455+129486A>G		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70239 AN: 151854 Hom.: 16816 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.463 AC: 70300 AN: 151972 Hom.: 16836 Cov.: 31 AF XY: 0.461 AC XY: 34220 AN XY: 74284

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.434

Alfa AF: 0.480 Hom.: 3337

Bravo AF: 0.455

Asia WGS AF: 0.298 AC: 1039 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.4
DANN	Benign	0.85

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: rs6450530; hg19: chr5-59059508; COSMIC: COSV58948817;