rs7717864

Variant names:

• chr5-60190941-G-A
• rs7717864
• ENST00000502484.6:c.-89-5254C>T

Variant summary

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

The NM_001165899.2(PDE4D):​c.-89-5254C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,940 control chromosomes in the GnomAD database, including 5,507 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 0.24 (5507 hom., cov: 32)
• Consequence: PDE4D NM_001165899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 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.-89-5254C>T		intron	N/A	NP_001159371.1	Q08499-11
	PDE4D	NM_001364599.1		c.-89-5254C>T		intron	N/A	NP_001351528.1	Q08499-11
	PDE4D	NM_001349241.2		c.-192-5254C>T		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.-89-5254C>T		intron	N/A	ENSP00000423094.2	Q08499-11
	PDE4D	ENST00000509355.5	TSL:1	n.158-5254C>T		intron	N/A
	PDE4D	ENST00000509368.6	TSL:1	n.-89-5254C>T		intron	N/A	ENSP00000423555.2	D6R9L4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35910 AN: 151822 Hom.: 5473 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.237 AC: 35992 AN: 151940 Hom.: 5507 Cov.: 32 AF XY: 0.234 AC XY: 17407 AN XY: 74280

African (AFR) AF: 0.442 AC: 18276 AN: 41386

American (AMR) AF: 0.158 AC: 2416 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3464

East Asian (EAS) AF: 0.158 AC: 814 AN: 5136

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1267 AN: 10572

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10971 AN: 67970

Other (OTH) AF: 0.221 AC: 466 AN: 2106

Alfa AF: 0.186 Hom.: 5255

Bravo AF: 0.245

Asia WGS AF: 0.199 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.92
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7717864;

hg19: chr5-59486768;