5-77181995-A-G

Variant names:

• chr5-77181995-A-G
• rs2928167
• ENST00000646262.1:c.-34+63474A>G

Variant summary

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

The ENST00000646262.1(PDE8B):​c.-34+63474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,806 control chromosomes in the GnomAD database, including 7,136 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 0.26 (7136 hom., cov: 31)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 10 publications found

Genes affected

PDE8B (HGNC:):

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_001349750.3	c.36+1509A>G		intron_variant	Intron 1 of 22		NP_001336679.1
PDE8B	NM_001376062.1	c.36+1509A>G		intron_variant	Intron 1 of 21		NP_001362991.1
PDE8B	NM_001349752.3	c.36+1509A>G		intron_variant	Intron 1 of 21		NP_001336681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000646262.1	c.-34+63474A>G		intron_variant	Intron 3 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39459 AN: 151688 Hom.: 7118 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.260 AC: 39534 AN: 151806 Hom.: 7136 Cov.: 31 AF XY: 0.270 AC XY: 19997 AN XY: 74200

African (AFR) AF: 0.426 AC: 17621 AN: 41338

American (AMR) AF: 0.249 AC: 3799 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.822 AC: 4216 AN: 5132

South Asian (SAS) AF: 0.322 AC: 1545 AN: 4798

European-Finnish (FIN) AF: 0.214 AC: 2251 AN: 10526

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9134 AN: 67964

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.176 Hom.: 604

Bravo AF: 0.273

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.68
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2928167; hg19: chr5-76477820;