5-60401981-A-C

Position:

• chr5-60401981-A-C

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-90+85961T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,072 control chromosomes in the GnomAD database, including 8,695 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 0.32 (8695 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-90+85961T>G		intron_variant			NP_001159371.1
PDE4D	NM_001349241.2	c.-193+85961T>G		intron_variant			NP_001336170.1
PDE4D	NM_001349243.2	c.-674+85961T>G		intron_variant			NP_001336172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+85961T>G		intron_variant		1		ENSP00000423094
PDE4D	ENST00000509355.5	n.157+85961T>G		intron_variant, non_coding_transcript_variant		1
PDE4D	ENST00000505507.6	c.-213+85961T>G		intron_variant		4		ENSP00000425910

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47956 AN: 151954 Hom.: 8678 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.316 AC: 47999 AN: 152072 Hom.: 8695 Cov.: 32 AF XY: 0.316 AC XY: 23456 AN XY: 74340

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.300

Alfa AF: 0.236 Hom.: 4283

Bravo AF: 0.327

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
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: rs918590; hg19: chr5-59697808;