rs12900078

Variant names:

• chr15-84980738-G-A
• rs12900078
• ENST00000310298.8:c.-190+236G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310298.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	NM_001243137.2		c.-31+53G>A		intron	N/A	NP_001230066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000310298.8	TSL:1	c.-190+236G>A		intron	N/A	ENSP00000311453.4
	PDE8A	ENST00000557957.5	TSL:2	c.-31+53G>A		intron	N/A	ENSP00000453808.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.129 AC: 8 AN: 62

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.0250 AC: 1039 AN: 41562

American (AMR) AF: 0.101 AC: 1552 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5180

South Asian (SAS) AF: 0.105 AC: 504 AN: 4810

European-Finnish (FIN) AF: 0.212 AC: 2243 AN: 10584

Middle Eastern (MID) AF: 0.217 AC: 63 AN: 290

European-Non Finnish (NFE) AF: 0.154 AC: 10441 AN: 67980

Other (OTH) AF: 0.119 AC: 251 AN: 2108

Alfa AF: 0.137 Hom.: 2029

Bravo AF: 0.102

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.8
DANN	Benign	0.86
PhyloP100		0.72
PromoterAI		-0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12900078; hg19: chr15-85523969;