rs16876573

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000338950.9(DTNBP1):c.870A>G(p.Pro290Pro) 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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

DTNBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 178772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.811+59A>G		intron_variant	Intron 9 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.811+59A>G		intron_variant	Intron 9 of 9	1	NM_032122.5	ENSP00000341680.6		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

GnomAD2 exomes

AF:

0.0356

AC:

8944

AN:

251342

AF XY:

0.0389

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 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

African (AFR)

AF:

0.0176

AC:

590

AN:

33472

American (AMR)

AF:

0.0243

AC:

1088

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0338

AC:

882

AN:

26118

East Asian (EAS)

AF:

0.000126

AC:

AN:

39688

South Asian (SAS)

AF:

0.0712

AC:

6143

AN:

86248

European-Finnish (FIN)

AF:

0.0125

AC:

666

AN:

53408

Middle Eastern (MID)

AF:

0.0527

AC:

304

AN:

5768

European-Non Finnish (NFE)

AF:

0.0436

AC:

48408

AN:

1111524

Other (OTH)

AF:

0.0383

AC:

2312

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

3779

7558

11338

15117

18896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1844

3688

5532

7376

9220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0321

AC:

4885

AN:

152260

Hom.:

116

Cov.:

AF XY:

0.0323

AC XY:

2407

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0185

AC:

770

AN:

41560

American (AMR)

AF:

0.0341

AC:

522

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3468

East Asian (EAS)

AF:

0.000581

AC:

AN:

5160

South Asian (SAS)

AF:

0.0693

AC:

334

AN:

4820

European-Finnish (FIN)

AF:

0.0121

AC:

129

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0426

AC:

2899

AN:

68022

Other (OTH)

AF:

0.0393

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

248

495

743

990

1238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0363

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.42

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over