rs930716

Variant names:

• chr15-84989010-A-G
• rs930716
• NM_002605.3:c.186+6662A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-84989010-A-G
• chr15-84989010-A-T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	NM_002605.3	MANE Select	c.186+6662A>G		intron	N/A	NP_002596.1	O60658-1
	PDE8A	NM_173454.1		c.186+6662A>G		intron	N/A	NP_775656.1	O60658-2
	PDE8A	NM_001243137.2		c.-31+8325A>G		intron	N/A	NP_001230066.1	O60658-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.186+6662A>G		intron	N/A	ENSP00000378056.1	O60658-1
	PDE8A	ENST00000310298.8	TSL:1	c.186+6662A>G		intron	N/A	ENSP00000311453.4	O60658-1
	PDE8A	ENST00000339708.9	TSL:1	c.186+6662A>G		intron	N/A	ENSP00000340679.5	O60658-2

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

African (AFR) AF: 0.234 AC: 9701 AN: 41496

American (AMR) AF: 0.539 AC: 8245 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2945 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2899 AN: 4822

European-Finnish (FIN) AF: 0.512 AC: 5423 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38563 AN: 67986

Other (OTH) AF: 0.475 AC: 1005 AN: 2114

Alfa AF: 0.538 Hom.: 38888

Bravo AF: 0.456

Asia WGS AF: 0.569 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.58
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: rs930716; hg19: chr15-85532241;