Variant rs16876738 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_032122.5(DTNBP1):c.355+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,610,846 control chromosomes in the GnomAD database, including 21,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1866 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19527 hom. )

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0400

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:

DTNBP1 (HGNC:):

DTNBP1 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=-0.86).

BP6

Variant 6-15627322-C-G is Benign according to our data. Variant chr6-15627322-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5 linkuse as main transcript	c.355+21G>C		intron_variant		ENST00000344537.10	NP_115498.2	Q96EV8-1A0A0S2Z5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 linkuse as main transcript	c.355+21G>C		intron_variant		1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22461

AN:

152010

Hom.:

1866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.170

AC:

42417

AN:

249564

Hom.:

4049

AF XY:

0.172

AC XY:

23261

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.0875

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.302

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.159

AC:

231800

AN:

1458718

Hom.:

19527

Cov.:

AF XY:

0.161

AC XY:

116865

AN XY:

725828

show subpopulations

Gnomad4 AFR exome

AF:

0.0881

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.148

AC:

22474

AN:

152128

Hom.:

1866

Cov.:

AF XY:

0.150

AC XY:

11182

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0864

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.126

Hom.:

328

Bravo

AF:

0.146

Asia WGS

AF:

0.225

AC:

784

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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