5-60481664-C-A

Variant names:

• chr5-60481664-C-A
• rs27224
• ENST00000502484.6:c.-90+6278G>T

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-90+6278G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,128 control chromosomes in the GnomAD database, including 1,345 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 0.11 (1345 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• 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

ENSG00000305967 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-90+6278G>T		intron_variant	Intron 1 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.-90+14475G>T		intron_variant	Intron 1 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-193+6278G>T		intron_variant	Intron 1 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+6278G>T		intron_variant	Intron 1 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.157+6278G>T		intron_variant	Intron 1 of 2	1
PDE4D	ENST00000505507.6	c.-213+6278G>T		intron_variant	Intron 1 of 3	4		ENSP00000425910.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17000 AN: 152010 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.112 AC: 17015 AN: 152128 Hom.: 1345 Cov.: 32 AF XY: 0.115 AC XY: 8576 AN XY: 74364

African (AFR) AF: 0.0446 AC: 1852 AN: 41514

American (AMR) AF: 0.154 AC: 2345 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1922 AN: 5158

South Asian (SAS) AF: 0.310 AC: 1494 AN: 4826

European-Finnish (FIN) AF: 0.0770 AC: 815 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7819 AN: 67996

Other (OTH) AF: 0.123 AC: 261 AN: 2116

Alfa AF: 0.107 Hom.: 1809

Bravo AF: 0.111

Asia WGS AF: 0.355 AC: 1230 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.38
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: rs27224; hg19: chr5-59777491;