5-60073967-A-G

Variant names:

• chr5-60073967-A-G
• rs1588265
• ENST00000502484.6:c.43-85250T>C

Variant summary

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

The NM_001165899.2(PDE4D):​c.43-85250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,750 control chromosomes in the GnomAD database, including 7,322 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 0.29 (7322 hom., cov: 31)
• Consequence: PDE4D NM_001165899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 64 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001165899.2		c.43-85250T>C		intron	N/A	NP_001159371.1	Q08499-11
	PDE4D	NM_001364599.1		c.43-85250T>C		intron	N/A	NP_001351528.1	Q08499-11
	PDE4D	NM_001349241.2		c.-61-69621T>C		intron	N/A	NP_001336170.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000502484.6	TSL:1	c.43-85250T>C		intron	N/A	ENSP00000423094.2	Q08499-11
	PDE4D	ENST00000509355.5	TSL:1	n.289-85250T>C		intron	N/A
	PDE4D	ENST00000509368.6	TSL:1	n.*184+73781T>C		intron	N/A	ENSP00000423555.2	D6R9L4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44631 AN: 151632 Hom.: 7304 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.294 AC: 44664 AN: 151750 Hom.: 7322 Cov.: 31 AF XY: 0.299 AC XY: 22186 AN XY: 74134

African (AFR) AF: 0.206 AC: 8520 AN: 41432

American (AMR) AF: 0.301 AC: 4585 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3840 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1639 AN: 4794

European-Finnish (FIN) AF: 0.307 AC: 3231 AN: 10522

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20842 AN: 67836

Other (OTH) AF: 0.316 AC: 662 AN: 2098

Alfa AF: 0.309 Hom.: 33979

Bravo AF: 0.290

Asia WGS AF: 0.547 AC: 1896 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.57
PhyloP100		-2.2
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: rs1588265; hg19: chr5-59369794;