chr5-60149310-C-T

Variant names:

• chr5-60149310-C-T
• rs983280
• ENST00000502484.6:c.42+36247G>A

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+36247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,020 control chromosomes in the GnomAD database, including 35,349 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 0.68 (35349 hom., cov: 31)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+36247G>A		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+36247G>A		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+36247G>A		intron_variant	Intron 2 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+36247G>A		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+36247G>A		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.*38-1416G>A		intron_variant	Intron 3 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102875 AN: 151902 Hom.: 35322 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.677 AC: 102940 AN: 152020 Hom.: 35349 Cov.: 31 AF XY: 0.674 AC XY: 50098 AN XY: 74288

African (AFR) AF: 0.689 AC: 28584 AN: 41464

American (AMR) AF: 0.691 AC: 10564 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2444 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1337 AN: 5150

South Asian (SAS) AF: 0.666 AC: 3193 AN: 4796

European-Finnish (FIN) AF: 0.700 AC: 7394 AN: 10558

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47126 AN: 67976

Other (OTH) AF: 0.664 AC: 1406 AN: 2116

Alfa AF: 0.687 Hom.: 109501

Bravo AF: 0.676

Asia WGS AF: 0.458 AC: 1595 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	0.48
DANN	Benign	0.47
PhyloP100		-1.4
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: rs983280; hg19: chr5-59445137;