chr5-77334964-T-C

Position:

• chr5-77334964-T-C

Variant summary

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

The NM_003719.5(PDE8B):​c.709-2263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,050 control chromosomes in the GnomAD database, including 17,399 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 0.47 (17399 hom., cov: 33)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.709-2263T>C		intron_variant		ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.709-2263T>C		intron_variant		1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71792 AN: 151932 Hom.: 17389 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.472 AC: 71841 AN: 152050 Hom.: 17399 Cov.: 33 AF XY: 0.472 AC XY: 35098 AN XY: 74322

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.467

Alfa AF: 0.470 Hom.: 2148

Bravo AF: 0.468

Asia WGS AF: 0.390 AC: 1354 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6887019; hg19: chr5-76630789;