5-59722069-A-G

Variant summary

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

The NM_001104631.2(PDE4D):c.455+171099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,028 control chromosomes in the GnomAD database, including 24,997 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 0.57 (24997 hom., cov: 33)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.455+171099T>C		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.455+171099T>C		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86135 AN: 151910 Hom.: 24964 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.567 AC: 86205 AN: 152028 Hom.: 24997 Cov.: 33 AF XY: 0.564 AC XY: 41924 AN XY: 74308

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.545

Alfa AF: 0.494 Hom.: 2335

Bravo AF: 0.560

Asia WGS AF: 0.432 AC: 1505 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	11
Dann	Benign	0.76

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: rs7701573; hg19: chr5-59017895; COSMIC: COSV58948426;