rs10514096

Variant names:

• chr5-77369359-G-A
• rs10514096
• NM_003719.5:c.1167+15953G>A

Variant summary

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

The NM_003719.5(PDE8B):​c.1167+15953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,004 control chromosomes in the GnomAD database, including 3,333 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 0.19 (3333 hom., cov: 30)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 7 publications found

Genes affected

PDE8B (HGNC:8794): (phosphodiesterase 8B) The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

PDE8B Gene-Disease associations (from GenCC):

• autosomal dominant striatal neurodegeneration type 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pigmented nodular adrenocortical disease, primary, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• primary pigmented nodular adrenocortical disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• striatal degeneration, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PDE8B (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003719.5. 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
	PDE8B	NM_003719.5	MANE Select	c.1167+15953G>A		intron	N/A	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.1230+15953G>A		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.1164+15953G>A		intron	N/A	NP_001336677.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.1167+15953G>A		intron	N/A	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000342343.8	TSL:1	c.1107+15953G>A		intron	N/A	ENSP00000345646.4	O95263-4
	PDE8B	ENST00000340978.7	TSL:1	c.1026+15953G>A		intron	N/A	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28558 AN: 151888 Hom.: 3331 Cov.: 30

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.188 AC: 28561 AN: 152004 Hom.: 3333 Cov.: 30 AF XY: 0.188 AC XY: 13978 AN XY: 74282

African (AFR) AF: 0.0543 AC: 2253 AN: 41486

American (AMR) AF: 0.176 AC: 2685 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3470

East Asian (EAS) AF: 0.111 AC: 573 AN: 5172

South Asian (SAS) AF: 0.193 AC: 925 AN: 4804

European-Finnish (FIN) AF: 0.252 AC: 2657 AN: 10540

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17900 AN: 67954

Other (OTH) AF: 0.200 AC: 420 AN: 2104

Alfa AF: 0.239 Hom.: 2444

Bravo AF: 0.174

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		0.095
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: rs10514096; hg19: chr5-76665184;