Variant 5-77426618-G-A 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.*64G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 830,778 control chromosomes in the GnomAD database, including 139,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30464 hom., cov: 32)

Exomes 𝑓: 0.56 ( 109207 hom. )

Consequence

PDE8B
NM_003719.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.564

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=-0.76).

BP6

Variant 5-77426618-G-A is Benign according to our data. Variant chr5-77426618-G-A is described in ClinVar as [Benign]. Clinvar id is 354179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_003719.5 linkuse as main transcript	c.*64G>A		3_prime_UTR_variant	22/22	ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10 linkuse as main transcript	c.*64G>A		3_prime_UTR_variant	22/22	1	NM_003719.5	ENSP00000264917	P1	O95263-1

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93974

AN:

152010

Hom.:

30412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.808

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.561

AC:

380897

AN:

678650

Hom.:

109207

Cov.:

AF XY:

0.562

AC XY:

204217

AN XY:

363334

show subpopulations

Gnomad4 AFR exome

AF:

0.811

Gnomad4 AMR exome

AF:

0.735

Gnomad4 ASJ exome

AF:

0.712

Gnomad4 EAS exome

AF:

0.604

Gnomad4 SAS exome

AF:

0.645

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.618

AC:

94084

AN:

152128

Hom.:

30464

Cov.:

AF XY:

0.618

AC XY:

45986

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.589

Gnomad4 SAS

AF:

0.654

Gnomad4 FIN

AF:

0.483

Gnomad4 NFE

AF:

0.507

Gnomad4 OTH

AF:

0.619

Alfa

AF:

0.519

Hom.:

14527

Bravo

AF:

0.646

Asia WGS

AF:

0.625

AC:

2175

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Striatal Degeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

-0.76

CADD

Benign

5.5

DANN

Benign

0.81

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