Variant 5-77210988-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003719.5(PDE8B):c.63C>T(p.Asp21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,541,786 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

PDE8B
NM_003719.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.365

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 5-77210988-C-T is Benign according to our data. Variant chr5-77210988-C-T is described in ClinVar as [Benign]. Clinvar id is 354145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.365 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000391 (543/1390084) while in subpopulation AFR AF= 0.0164 (475/28908). AF 95% confidence interval is 0.0152. There are 2 homozygotes in gnomad4_exome. There are 234 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 606 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8B	NM_003719.5 linkuse as main transcript	c.63C>T	p.Asp21=	synonymous_variant	1/22	ENST00000264917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8B	ENST00000264917.10 linkuse as main transcript	c.63C>T	p.Asp21=	synonymous_variant	1/22	1	NM_003719.5	P1	O95263-1

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

604

AN:

151594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.000637

AC:

106

AN:

166306

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

94042

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000415

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.000256

GnomAD4 exome

AF:

0.000391

AC:

543

AN:

1390084

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

234

AN XY:

690654

show subpopulations

Gnomad4 AFR exome

AF:

0.0164

Gnomad4 AMR exome

AF:

0.000468

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.000660

GnomAD4 genome

AF:

0.00399

AC:

606

AN:

151702

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

276

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.00454

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

clinical testing

Invitae

Dec 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

9.6

DANN

Benign

0.97

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