rs27178

Positions:

• chr5-59291199-A-G
• chr5-59291199-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.456-75231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,918 control chromosomes in the GnomAD database, including 25,168 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 0.56 (25168 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.456-75231T>C		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-75231T>C		intron_variant		1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85292 AN: 151800 Hom.: 25135 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.562 AC: 85375 AN: 151918 Hom.: 25168 Cov.: 32 AF XY: 0.564 AC XY: 41845 AN XY: 74222

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.536

Alfa AF: 0.506 Hom.: 2450

Bravo AF: 0.580

Asia WGS AF: 0.639 AC: 2219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.81
DANN	Benign	0.38

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: rs27178; hg19: chr5-58587025;