5-77426624-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003719.5(PDE8B):c.*70C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 791,858 control chromosomes in the GnomAD database, including 819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (111 hom., cov: 32)
  • Exomes 𝑓: 0.041 (708 hom.)
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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]

WDR41 (HGNC:25601): (WD repeat domain 41) Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 5-77426624-C-T is Benign according to our data. Variant chr5-77426624-C-T is described in ClinVar as [Benign]. Clinvar id is 354180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5	c.*70C>T		3_prime_UTR_variant	22/22	ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10	c.*70C>T		3_prime_UTR_variant	22/22	1	NM_003719.5	P1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4871 AN: 152166 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.00891

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0408 AC: 26075 AN: 639574 Hom.: 708 Cov.: 8 AF XY: 0.0411 AC XY: 14104 AN XY: 343480

Gnomad4 AFR exome AF: 0.00892

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0311

Gnomad4 EAS exome AF: 0.0000295

Gnomad4 SAS exome AF: 0.0283

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0511

Gnomad4 OTH exome AF: 0.0381

GnomAD4 genome AF: 0.0320 AC: 4875 AN: 152284 Hom.: 111 Cov.: 32 AF XY: 0.0305 AC XY: 2273 AN XY: 74472

Gnomad4 AFR AF: 0.00900

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0506

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0441 Hom.: 26

Bravo AF: 0.0296

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant striatal neurodegeneration type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	9.9
Dann	Benign	0.80

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: rs78676901; hg19: chr5-76722449;