rs2928163

Variant names:

• chr5-77192420-G-A
• rs2928163
• ENST00000646262.1:c.-34+73899G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77192420-G-A
• chr5-77192420-G-T

Variant summary

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

The ENST00000646262.1(PDE8B):​c.-34+73899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,092 control chromosomes in the GnomAD database, including 40,617 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 0.72 (40617 hom., cov: 31)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646262.1. 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_001349750.3		c.36+11934G>A		intron	N/A	NP_001336679.1
	PDE8B	NM_001376062.1		c.36+11934G>A		intron	N/A	NP_001362991.1
	PDE8B	NM_001349752.3		c.36+11934G>A		intron	N/A	NP_001336681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000646262.1		c.-34+73899G>A		intron	N/A	ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109688 AN: 151974 Hom.: 40562 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.722 AC: 109803 AN: 152092 Hom.: 40617 Cov.: 31 AF XY: 0.728 AC XY: 54152 AN XY: 74342

African (AFR) AF: 0.854 AC: 35455 AN: 41494

American (AMR) AF: 0.611 AC: 9343 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1979 AN: 3466

East Asian (EAS) AF: 0.959 AC: 4960 AN: 5174

South Asian (SAS) AF: 0.774 AC: 3724 AN: 4814

European-Finnish (FIN) AF: 0.770 AC: 8142 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43891 AN: 67968

Other (OTH) AF: 0.707 AC: 1492 AN: 2110

Alfa AF: 0.705 Hom.: 7352

Bravo AF: 0.713

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.72
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs2928163; hg19: chr5-76488245;