rs2962975

chr5-60161151-C-T

Variant summary

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

The ENST00000502484.6(PDE4D):c.42+24406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,926 control chromosomes in the GnomAD database, including 35,152 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 0.67 (35152 hom., cov: 31)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.42+24406G>A		intron_variant
PDE4D	NM_001349241.2	c.-62+24406G>A		intron_variant
PDE4D	NM_001349243.2	c.-543+24406G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+24406G>A		intron_variant		1
PDE4D	ENST00000509368.6	c.43-334G>A		intron_variant, NMD_transcript_variant		1
PDE4D	ENST00000509355.5	n.288+24406G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102463 AN: 151808 Hom.: 35120 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.675 AC: 102538 AN: 151926 Hom.: 35152 Cov.: 31 AF XY: 0.672 AC XY: 49885 AN XY: 74270

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.663

Alfa AF: 0.687 Hom.: 5278

Bravo AF: 0.674

Asia WGS AF: 0.445 AC: 1551 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2962975; hg19: chr5-59456978;