rs42222

chr5-60419787-C-Achr5-60419787-C-Gchr5-60419787-C-T

Variant summary

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

The ENST00000502484.6(PDE4D):c.-90+68155G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,100 control chromosomes in the GnomAD database, including 1,405 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 0.11 (1405 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.-90+68155G>T		intron_variant
PDE4D	NM_001349241.2	c.-193+68155G>T		intron_variant
PDE4D	NM_001349243.2	c.-674+68155G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+68155G>T		intron_variant		1
PDE4D	ENST00000509355.5	n.157+68155G>T		intron_variant, non_coding_transcript_variant		1
PDE4D	ENST00000505507.6	c.-213+68155G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16950 AN: 151982 Hom.: 1392 Cov.: 32

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.112 AC: 16969 AN: 152100 Hom.: 1405 Cov.: 32 AF XY: 0.118 AC XY: 8784 AN XY: 74344

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0970 Hom.: 97

Bravo AF: 0.109

Asia WGS AF: 0.380 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs42222; hg19: chr5-59715614;