5-60491814-T-C

Position:

• chr5-60491814-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364599.1(PDE4D):​c.-90+4325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,620 control chromosomes in the GnomAD database, including 1,354 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 0.13 (1354 hom., cov: 32)
• Consequence: PDE4D NM_001364599.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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]

PART1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001364599.1	c.-90+4325A>G		intron_variant			NP_001351528.1
PDE4D	XM_024446110.2	c.-90+30237A>G		intron_variant			XP_024301878.1
PDE4D	XM_024446112.2	c.-90+30237A>G		intron_variant			XP_024301880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PART1	ENST00000667192.1	n.2580T>C		non_coding_transcript_exon_variant	2/2
PART1	ENST00000504876.2	n.217+3391T>C		intron_variant		2
PDE4D	ENST00000506510.6	n.70+30237A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19442 AN: 151502 Hom.: 1353 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0901

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.128 AC: 19447 AN: 151620 Hom.: 1354 Cov.: 32 AF XY: 0.125 AC XY: 9282 AN XY: 74132

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0900

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0529 Hom.: 75

Bravo AF: 0.125

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12153798; hg19: chr5-59787641;