Variant 5-77426624-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Variant links:

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]

PDE8B links:

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]

WDR41 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	c.*70C>T		3_prime_UTR_variant	22/22	1	NM_003719.5	P1	O95263-1

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4871

AN:

152166

Hom.:

110

Cov.:

show subpopulations

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.:

AF XY:

0.0411

AC XY:

14104

AN XY:

343480

show subpopulations

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.:

AF XY:

0.0305

AC XY:

2273

AN XY:

74472

show subpopulations

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.:

Bravo

AF:

0.0296

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over