chr5-77224687-G-T

Variant names:

• chr5-77224687-G-T
• rs12520862
• NM_003719.5:c.339+13423G>T

Variant summary

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

The NM_003719.5(PDE8B):​c.339+13423G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,108 control chromosomes in the GnomAD database, including 2,027 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 0.16 (2027 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.311 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_003719.5	MANE Select	c.339+13423G>T		intron	N/A	NP_003710.1
	PDE8B	NM_001349749.3		c.339+13423G>T		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.339+13423G>T		intron	N/A	NP_001336677.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.339+13423G>T		intron	N/A	ENSP00000264917.6
	PDE8B	ENST00000342343.8	TSL:1	c.339+13423G>T		intron	N/A	ENSP00000345646.4
	PDE8B	ENST00000340978.7	TSL:1	c.339+13423G>T		intron	N/A	ENSP00000345446.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24231 AN: 151990 Hom.: 2022 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.159 AC: 24245 AN: 152108 Hom.: 2027 Cov.: 32 AF XY: 0.163 AC XY: 12149 AN XY: 74348

African (AFR) AF: 0.163 AC: 6780 AN: 41506

American (AMR) AF: 0.146 AC: 2232 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1676 AN: 5168

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4822

European-Finnish (FIN) AF: 0.188 AC: 1986 AN: 10550

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9572 AN: 67988

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.145 Hom.: 2547

Bravo AF: 0.157

Asia WGS AF: 0.266 AC: 923 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.64
PhyloP100		-0.29
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: rs12520862; hg19: chr5-76520512;