rs12909130

Variant names:

• chr15-85047270-T-C
• rs12909130
• NM_002605.3:c.187-17100T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-85047270-T-C
• chr15-85047270-T-G

Variant summary

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

The NM_002605.3(PDE8A):​c.187-17100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,202 control chromosomes in the GnomAD database, including 4,324 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 0.21 (4324 hom., cov: 32)
• Consequence: PDE8A NM_002605.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 8 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3	c.187-17100T>C		intron_variant	Intron 1 of 21	ENST00000394553.6	NP_002596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6	c.187-17100T>C		intron_variant	Intron 1 of 21	1	NM_002605.3	ENSP00000378056.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31587 AN: 152084 Hom.: 4332 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.207 AC: 31560 AN: 152202 Hom.: 4324 Cov.: 32 AF XY: 0.206 AC XY: 15336 AN XY: 74416

African (AFR) AF: 0.0489 AC: 2033 AN: 41560

American (AMR) AF: 0.203 AC: 3106 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3472

East Asian (EAS) AF: 0.0507 AC: 263 AN: 5190

South Asian (SAS) AF: 0.151 AC: 729 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3171 AN: 10564

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20047 AN: 67996

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.263 Hom.: 3019

Bravo AF: 0.195

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.5
DANN	Benign	0.90
PhyloP100		0.25
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: rs12909130; hg19: chr15-85590501;