rs2910830

Positions:

• chr5-60171376-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+14181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,768 control chromosomes in the GnomAD database, including 27,842 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 0.60 (27842 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.42+14181C>T		intron_variant
PDE4D	NM_001349241.2	c.-62+14181C>T		intron_variant
PDE4D	NM_001349243.2	c.-543+14181C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+14181C>T		intron_variant		1
PDE4D	ENST00000509368.6	c.43-10559C>T		intron_variant, NMD_transcript_variant		1
PDE4D	ENST00000509355.5	n.288+14181C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91076 AN: 151650 Hom.: 27828 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.600 AC: 91118 AN: 151768 Hom.: 27842 Cov.: 32 AF XY: 0.598 AC XY: 44333 AN XY: 74146

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.592

Alfa AF: 0.627 Hom.: 60854

Bravo AF: 0.597

Asia WGS AF: 0.411 AC: 1431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2910830; hg19: chr5-59467203;