5-60178388-G-A

Position:

• chr5-60178388-G-A

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+7169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 152,150 control chromosomes in the GnomAD database, including 289 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 0.058 (289 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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 (SAS) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+7169C>T		intron_variant			NP_001159371.1
PDE4D	NM_001349241.2	c.-62+7169C>T		intron_variant			NP_001336170.1
PDE4D	NM_001349243.2	c.-543+7169C>T		intron_variant			NP_001336172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+7169C>T		intron_variant		1		ENSP00000423094
PDE4D	ENST00000509368.6	c.42+7169C>T		intron_variant, NMD_transcript_variant		1		ENSP00000423555
PDE4D	ENST00000509355.5	n.288+7169C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8828 AN: 152032 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0580 AC: 8832 AN: 152150 Hom.: 289 Cov.: 32 AF XY: 0.0574 AC XY: 4270 AN XY: 74382

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0611 Hom.: 418

Bravo AF: 0.0571

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13158277; hg19: chr5-59474215;