rs12900078

Positions:

• chr15-84980738-G-A

Variant summary

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

The ENST00000310298.8(PDE8A):​c.-190+236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,276 control chromosomes in the GnomAD database, including 1,309 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 (1309 hom., cov: 33)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: PDE8A ENST00000310298.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8A	NM_001243137.2	c.-31+53G>A		intron_variant			NP_001230066.1
PDE8A	XM_047432657.1	c.-31+53G>A		intron_variant			XP_047288613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000310298.8	c.-190+236G>A		intron_variant		1		ENSP00000311453
PDE8A	ENST00000557957.5	c.-31+53G>A		intron_variant		2		ENSP00000453808	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17293 AN: 152080 Hom.: 1312 Cov.: 33

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.122 AC: 9 AN: 74 Hom.: 0 AF XY: 0.121 AC XY: 7 AN XY: 58

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.114 AC: 17286 AN: 152202 Hom.: 1309 Cov.: 33 AF XY: 0.117 AC XY: 8705 AN XY: 74410

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.119

Alfa AF: 0.144 Hom.: 1675

Bravo AF: 0.102

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.8
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12900078; hg19: chr15-85523969;