Variant 6-15593088-GAAAAA-GAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_032122.5(DTNBP1):c.489-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,236,686 control chromosomes in the GnomAD database, including 2,611 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.18 ( 2285 hom., cov: 28)

Exomes 𝑓: 0.21 ( 326 hom. )

Consequence

DTNBP1
NM_032122.5 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

DTNBP1 (HGNC:17328): (dystrobrevin binding protein 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-15593088-G-GA is Benign according to our data. Variant chr6-15593088-G-GA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355969.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.489-8dupT		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000344537.10	NP_115498.2	Q96EV8-1A0A0S2Z5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 link	c.489-8_489-7insT		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

24111

AN:

135696

Hom.:

2288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0721

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.0776

Gnomad MID

AF:

0.154

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.210

AC:

230914

AN:

1100954

Hom.:

326

Cov.:

AF XY:

0.209

AC XY:

114865

AN XY:

548704

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.286

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.178

AC:

24117

AN:

135732

Hom.:

2285

Cov.:

AF XY:

0.179

AC XY:

11698

AN XY:

65400

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.0776

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.188

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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