rs921942

Positions:

• chr5-59492031-A-C
• chr5-59492031-A-T

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-276063T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,960 control chromosomes in the GnomAD database, including 22,613 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 0.53 (22613 hom., cov: 31)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

PDE4D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.456-276063T>G		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-276063T>G		intron_variant		1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80699 AN: 151842 Hom.: 22573 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.532 AC: 80793 AN: 151960 Hom.: 22613 Cov.: 31 AF XY: 0.525 AC XY: 39033 AN XY: 74280

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.518

Alfa AF: 0.456 Hom.: 1913

Bravo AF: 0.544

Asia WGS AF: 0.264 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.49

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: rs921942; hg19: chr5-58787857;