chr5-77100092-C-A

Position:

• chr5-77100092-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414622.1(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 NM_001414622.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

ENSG00000284762 (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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-236+12473C>A		intron_variant			NP_001401551.1
PDE8B	NM_001414623.1	c.-236+12473C>A		intron_variant			NP_001401552.1
ZBED3-AS1	NR_024398.2	n.323+12473C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000284762	ENST00000646262.1	c.-236+12473C>A		intron_variant				ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.1810-18228C>A		intron_variant				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

Gnomad4 NFE exome AF: 0.125

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

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.230

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13154602; hg19: chr5-76395917;