rs8032301

Variant names:

• chr15-85092659-T-C
• rs8032301
• NM_002605.3:c.852+1478T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002605.3(PDE8A):​c.852+1478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,766 control chromosomes in the GnomAD database, including 18,986 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 0.49 (18986 hom., cov: 29)
• Consequence: PDE8A NM_002605.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002605.3. 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_002605.3	MANE Select	c.852+1478T>C		intron	N/A	NP_002596.1
	PDE8A	NM_173454.1		c.714+3243T>C		intron	N/A	NP_775656.1
	PDE8A	NM_001243137.2		c.636+1478T>C		intron	N/A	NP_001230066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.852+1478T>C		intron	N/A	ENSP00000378056.1
	PDE8A	ENST00000310298.8	TSL:1	c.852+1478T>C		intron	N/A	ENSP00000311453.4
	PDE8A	ENST00000339708.9	TSL:1	c.714+3243T>C		intron	N/A	ENSP00000340679.5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74902 AN: 151648 Hom.: 18975 Cov.: 29

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.494 AC: 74943 AN: 151766 Hom.: 18986 Cov.: 29 AF XY: 0.492 AC XY: 36470 AN XY: 74138

African (AFR) AF: 0.623 AC: 25773 AN: 41370

American (AMR) AF: 0.458 AC: 6994 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2188 AN: 5132

South Asian (SAS) AF: 0.440 AC: 2113 AN: 4798

European-Finnish (FIN) AF: 0.450 AC: 4732 AN: 10526

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29583 AN: 67906

Other (OTH) AF: 0.491 AC: 1037 AN: 2110

Alfa AF: 0.456 Hom.: 40322

Bravo AF: 0.500

Asia WGS AF: 0.432 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.44
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8032301; hg19: chr15-85635890;