rs13158277

Variant names:

• chr5-60178388-G-A
• rs13158277
• ENST00000502484.6:c.42+7169C>T

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+7169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 152,150 control chromosomes in the GnomAD database, including 289 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 0.058 (289 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0602 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.42+7169C>T		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.42+7169C>T		intron	N/A	NP_001351528.1
	PDE4D	NM_001349241.2		c.-62+7169C>T		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.42+7169C>T		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000509355.5	TSL:1	n.288+7169C>T		intron	N/A
	PDE4D	ENST00000509368.6	TSL:1	n.42+7169C>T		intron	N/A	ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8828 AN: 152032 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0580 AC: 8832 AN: 152150 Hom.: 289 Cov.: 32 AF XY: 0.0574 AC XY: 4270 AN XY: 74382

African (AFR) AF: 0.0618 AC: 2568 AN: 41536

American (AMR) AF: 0.0458 AC: 699 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3470

East Asian (EAS) AF: 0.0476 AC: 246 AN: 5172

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4824

European-Finnish (FIN) AF: 0.0489 AC: 517 AN: 10572

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4130 AN: 67986

Other (OTH) AF: 0.0563 AC: 119 AN: 2114

Alfa AF: 0.0605 Hom.: 536

Bravo AF: 0.0571

Asia WGS AF: 0.0440 AC: 155 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	1.3
DANN	Benign	0.27
PhyloP100		-0.014
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: rs13158277; hg19: chr5-59474215;