rs13154602

Variant names:

• chr5-77100092-C-A
• rs13154602
• ENST00000646262.1:c.-236+12473C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77100092-C-A
• chr5-77100092-C-T

Variant summary

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

The ENST00000646262.1(PDE8B):​c.-236+12473C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,210 control chromosomes in the GnomAD database, including 4,537 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 0.22 (4537 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 4 publications found

Genes affected

PDE8B (HGNC:):

ZBED3-AS1 (HGNC:44188): (ZBED3 antisense RNA 1)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-236+12473C>A		intron_variant	Intron 1 of 22		NP_001401551.1
PDE8B	NM_001414623.1	c.-236+12473C>A		intron_variant	Intron 2 of 23		NP_001401552.1
ZBED3-AS1	NR_024398.2	n.323+12473C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000646262.1	c.-236+12473C>A		intron_variant	Intron 2 of 23			ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.1810-18228C>A		intron_variant	Intron 13 of 15			ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34090 AN: 152084 Hom.: 4533 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.224 AC: 34107 AN: 152202 Hom.: 4537 Cov.: 32 AF XY: 0.223 AC XY: 16567 AN XY: 74416

African (AFR) AF: 0.0782 AC: 3248 AN: 41552

American (AMR) AF: 0.342 AC: 5238 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5184

South Asian (SAS) AF: 0.163 AC: 789 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2574 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19352 AN: 67980

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.214 Hom.: 726

Bravo AF: 0.228

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		0.050

Splicing

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

Other links and lift over

dbSNP: rs13154602; hg19: chr5-76395917;