5-77154365-T-C

Position:

• chr5-77154365-T-C

Variant summary

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

The NM_001414622.1(PDE8B):​c.-34+35844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,230 control chromosomes in the GnomAD database, including 21,357 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 0.49 (21357 hom., cov: 33)
• Consequence: PDE8B NM_001414622.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-34+35844T>C		intron_variant			NP_001401551.1
PDE8B	NM_001414623.1	c.-34+35844T>C		intron_variant			NP_001401552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000284762	ENST00000646262.1	c.-34+35844T>C		intron_variant				ENSP00000493971.1
ZBED3-AS1	ENST00000508401.1	n.201-10996T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74089 AN: 152112 Hom.: 21351 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.487 AC: 74093 AN: 152230 Hom.: 21357 Cov.: 33 AF XY: 0.497 AC XY: 36973 AN XY: 74436

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.518

Alfa AF: 0.576 Hom.: 12013

Bravo AF: 0.463

Asia WGS AF: 0.720 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6864250; hg19: chr5-76450190;