ENST00000502484.6:c.-90+85961T>G

Variant names:

• chr5-60401981-A-C
• rs918590
• ENST00000502484.6:c.-90+85961T>G

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-90+85961T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,072 control chromosomes in the GnomAD database, including 8,695 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 0.32 (8695 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 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.-90+85961T>G		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.-90+94158T>G		intron	N/A	NP_001351528.1
	PDE4D	NM_001349241.2		c.-193+85961T>G		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.-90+85961T>G		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000509355.5	TSL:1	n.157+85961T>G		intron	N/A
	PDE4D	ENST00000505507.6	TSL:4	c.-213+85961T>G		intron	N/A	ENSP00000425910.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47956 AN: 151954 Hom.: 8678 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.316 AC: 47999 AN: 152072 Hom.: 8695 Cov.: 32 AF XY: 0.316 AC XY: 23456 AN XY: 74340

African (AFR) AF: 0.472 AC: 19555 AN: 41432

American (AMR) AF: 0.279 AC: 4273 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2739 AN: 5156

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4812

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15593 AN: 67996

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.241 Hom.: 5223

Bravo AF: 0.327

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.10
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: rs918590; hg19: chr5-59697808;