5-77154365-T-C

Variant names:

• chr5-77154365-T-C
• rs6864250
• ENST00000646262.1:c.-34+35844T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414622.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_001414622.1		c.-34+35844T>C		intron	N/A	NP_001401551.1	A0A2R8Y4E6
	PDE8B	NM_001414623.1		c.-34+35844T>C		intron	N/A	NP_001401552.1	A0A2R8Y4E6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000646262.1		c.-34+35844T>C		intron	N/A	ENSP00000493971.1	A0A2R8Y4E6
	ZBED3-AS1	ENST00000508401.1	TSL:2	n.201-10996T>C		intron	N/A

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

African (AFR) AF: 0.160 AC: 6660 AN: 41558

American (AMR) AF: 0.540 AC: 8258 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3470

East Asian (EAS) AF: 0.877 AC: 4549 AN: 5186

South Asian (SAS) AF: 0.635 AC: 3064 AN: 4828

European-Finnish (FIN) AF: 0.628 AC: 6645 AN: 10586

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40955 AN: 67996

Other (OTH) AF: 0.518 AC: 1095 AN: 2112

Alfa AF: 0.573 Hom.: 13336

Bravo AF: 0.463

Asia WGS AF: 0.720 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.46
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs6864250; hg19: chr5-76450190;