rs16876573

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000338950.9(DTNBP1):c.870A>G(p.Pro290=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,613,570 control chromosomes in the GnomAD database, including 1,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 116 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1502 hom. )

Consequence

DTNBP1
ENST00000338950.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.161

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-15524467-T-C is Benign according to our data. Variant chr6-15524467-T-C is described in ClinVar as [Benign]. Clinvar id is 178772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-15524467-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.161 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5 linkuse as main transcript	c.811+59A>G		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10 linkuse as main transcript	c.811+59A>G		intron_variant		1	NM_032122.5	P1	Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4870

AN:

152142

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0426

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0356

AC:

8944

AN:

251342

Hom.:

232

AF XY:

0.0389

AC XY:

5281

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0342

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0711

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0426

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0413

AC:

60398

AN:

1461310

Hom.:

1502

Cov.:

AF XY:

0.0422

AC XY:

30670

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0338

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0712

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.0436

Gnomad4 OTH exome

AF:

0.0383

GnomAD4 genome

AF:

0.0321

AC:

4885

AN:

152260

Hom.:

116

Cov.:

AF XY:

0.0323

AC XY:

2407

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.0341

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0693

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0426

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0387

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0458

EpiControl

AF:

0.0481

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Pro290Pro in exon 9A of DTNBP1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 4.3% (373/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs16876573). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

1.7

Dann

Benign

0.42

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