rs27224

chr5-60481664-C-Achr5-60481664-C-G

Variant summary

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

The ENST00000502484.6(PDE4D):c.-90+6278G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,128 control chromosomes in the GnomAD database, including 1,345 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 0.11 (1345 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.-90+6278G>T		intron_variant
PDE4D	NM_001349241.2	c.-193+6278G>T		intron_variant
PDE4D	NM_001349243.2	c.-674+6278G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+6278G>T		intron_variant		1
PDE4D	ENST00000509355.5	n.157+6278G>T		intron_variant, non_coding_transcript_variant		1
PDE4D	ENST00000505507.6	c.-213+6278G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17000 AN: 152010 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.112 AC: 17015 AN: 152128 Hom.: 1345 Cov.: 32 AF XY: 0.115 AC XY: 8576 AN XY: 74364

Gnomad4 AFR AF: 0.0446

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.123

Alfa AF: 0.112 Hom.: 1106

Bravo AF: 0.111

Asia WGS AF: 0.355 AC: 1230 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs27224; hg19: chr5-59777491;