5-60100815-T-G

Position:

• chr5-60100815-T-G

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+84742A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,120 control chromosomes in the GnomAD database, including 1,499 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 0.14 (1499 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.42+84742A>C		intron_variant
PDE4D	NM_001349241.2	c.-62+84742A>C		intron_variant
PDE4D	NM_001349243.2	c.-543+84742A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+84742A>C		intron_variant		1
PDE4D	ENST00000509368.6	c.*184+46933A>C		intron_variant, NMD_transcript_variant		1
PDE4D	ENST00000509355.5	n.288+84742A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21001 AN: 152002 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.138 AC: 20998 AN: 152120 Hom.: 1499 Cov.: 32 AF XY: 0.138 AC XY: 10295 AN XY: 74402

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0746 Hom.: 104

Bravo AF: 0.129

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396476; hg19: chr5-59396642;