ENST00000502484.6:c.43-37287G>C

Variant names:

• chr5-60026004-C-G
• rs1995780
• ENST00000502484.6:c.43-37287G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502484.6(PDE4D):​c.43-37287G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,990 control chromosomes in the GnomAD database, including 18,478 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 0.49 (18478 hom., cov: 33)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• acrodysostosis 2 with or without hormone resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• acrodysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrodysostosis with multiple hormone resistance

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chromosome 5q12 deletion syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000248935 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502484.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001165899.2		c.43-37287G>C		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.43-37287G>C		intron	N/A	NP_001351528.1
	PDE4D	NM_001349241.2		c.-61-21658G>C		intron	N/A	NP_001336170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000502484.6	TSL:1	c.43-37287G>C		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000509355.5	TSL:1	n.289-37287G>C		intron	N/A
	PDE4D	ENST00000509368.6	TSL:1	n.*185-37287G>C		intron	N/A	ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73962 AN: 151872 Hom.: 18447 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.487 AC: 74044 AN: 151990 Hom.: 18478 Cov.: 33 AF XY: 0.491 AC XY: 36434 AN XY: 74278

African (AFR) AF: 0.510 AC: 21138 AN: 41450

American (AMR) AF: 0.437 AC: 6678 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1557 AN: 3462

East Asian (EAS) AF: 0.823 AC: 4261 AN: 5176

South Asian (SAS) AF: 0.564 AC: 2724 AN: 4828

European-Finnish (FIN) AF: 0.459 AC: 4837 AN: 10542

Middle Eastern (MID) AF: 0.528 AC: 153 AN: 290

European-Non Finnish (NFE) AF: 0.462 AC: 31387 AN: 67960

Other (OTH) AF: 0.490 AC: 1033 AN: 2108

Alfa AF: 0.476 Hom.: 2197

Bravo AF: 0.480

Asia WGS AF: 0.700 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1995780; hg19: chr5-59321831;