rs153067

Variant names:

• chr5-60467572-G-A
• rs153067
• ENST00000502484.6:c.-90+20370C>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+20370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,000 control chromosomes in the GnomAD database, including 15,750 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 0.44 (15750 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-90+20370C>T		intron_variant	Intron 1 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.-90+28567C>T		intron_variant	Intron 1 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-193+20370C>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+20370C>T		intron_variant	Intron 1 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.157+20370C>T		intron_variant	Intron 1 of 2	1
PDE4D	ENST00000505507.6	c.-213+20370C>T		intron_variant	Intron 1 of 3	4		ENSP00000425910.2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66295 AN: 151882 Hom.: 15699 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.437 AC: 66391 AN: 152000 Hom.: 15750 Cov.: 32 AF XY: 0.434 AC XY: 32232 AN XY: 74298

African (AFR) AF: 0.619 AC: 25639 AN: 41448

American (AMR) AF: 0.372 AC: 5668 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2910 AN: 5168

South Asian (SAS) AF: 0.592 AC: 2860 AN: 4830

European-Finnish (FIN) AF: 0.274 AC: 2900 AN: 10574

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23999 AN: 67948

Other (OTH) AF: 0.412 AC: 868 AN: 2108

Alfa AF: 0.428 Hom.: 2593

Bravo AF: 0.447

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.011
DANN	Benign	0.46
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs153067; hg19: chr5-59763399;