rs930716

chr15-84989010-A-Gchr15-84989010-A-T

Variant summary

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

The NM_002605.3(PDE8A):c.186+6662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,134 control chromosomes in the GnomAD database, including 18,043 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 0.47 (18043 hom., cov: 33)
• Consequence: PDE8A NM_002605.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8A	NM_002605.3	c.186+6662A>G		intron_variant		ENST00000394553.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8A	ENST00000394553.6	c.186+6662A>G		intron_variant		1	NM_002605.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70763 AN: 152016 Hom.: 18022 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.465 AC: 70809 AN: 152134 Hom.: 18043 Cov.: 33 AF XY: 0.467 AC XY: 34744 AN XY: 74376

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.475

Alfa AF: 0.546 Hom.: 31531

Bravo AF: 0.456

Asia WGS AF: 0.569 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.72

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: rs930716; hg19: chr15-85532241;