Variant 5-77426991-A-G 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.*437A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 193,134 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 96 hom., cov: 32)

Exomes 𝑓: 0.028 ( 62 hom. )

Consequence

PDE8B
NM_003719.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.278

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:

ENSG00000284762 (HGNC:):

ENSG00000284762 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=-0.87).

BP6

Variant 5-77426991-A-G is Benign according to our data. Variant chr5-77426991-A-G is described in ClinVar as [Benign]. Clinvar id is 354185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 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.*437A>G		3_prime_UTR_variant	22/22	ENST00000264917.10	NP_003710.1	O95263-1B3KN77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10 linkuse as main transcript	c.*437A>G		3_prime_UTR_variant	22/22	1	NM_003719.5	ENSP00000264917.6		O95263-1
ENSG00000284762	ENST00000646262.1 linkuse as main transcript	c.*437A>G		3_prime_UTR_variant	24/24			ENSP00000493971.1		A0A2R8Y4E6

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3589

AN:

150824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0394

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.0602

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.00957

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0279

GnomAD4 exome

AF:

0.0278

AC:

1171

AN:

42174

Hom.:

Cov.:

AF XY:

0.0335

AC XY:

721

AN XY:

21550

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0553

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.00766

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0238

AC:

3587

AN:

150960

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1946

AN XY:

73786

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.0548

Gnomad4 EAS

AF:

0.0599

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.00957

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0276

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.0660

AC:

230

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

-0.87

CADD

Benign

0.95

DANN

Benign

0.61

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