rs17470454

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032122.5(DTNBP1):c.814C>T(p.Pro272Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.049 in 1,613,910 control chromosomes in the GnomAD database, including 2,473 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 201 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2272 hom. )

Consequence

DTNBP1
NM_032122.5 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.17

Publications

23 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016671717).

BP6

Variant 6-15523217-G-A is Benign according to our data. Variant chr6-15523217-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.814C>T	p.Pro272Ser	missense_variant, splice_region_variant	Exon 10 of 10	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.814C>T	p.Pro272Ser	missense_variant, splice_region_variant	Exon 10 of 10	1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6328

AN:

152210

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0579

Gnomad OTH

AF:

0.0358

GnomAD2 exomes

AF:

0.0425

AC:

10675

AN:

251402

AF XY:

0.0423

show subpopulations

Gnomad AFR exome

AF:

0.00815

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0422

GnomAD4 exome

AF:

0.0498

AC:

72806

AN:

1461582

Hom.:

2272

Cov.:

AF XY:

0.0486

AC XY:

35302

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00777

AC:

260

AN:

33478

American (AMR)

AF:

0.0167

AC:

747

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0142

AC:

372

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00486

AC:

419

AN:

86196

European-Finnish (FIN)

AF:

0.124

AC:

6597

AN:

53412

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0557

AC:

61917

AN:

1111784

Other (OTH)

AF:

0.0405

AC:

2447

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

3516

7033

10549

14066

17582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2152

4304

6456

8608

10760

<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:

0.0415

AC:

6328

AN:

152328

Hom.:

201

Cov.:

AF XY:

0.0429

AC XY:

3198

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00943

AC:

392

AN:

41560

American (AMR)

AF:

0.0258

AC:

395

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.00622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.130

AC:

1376

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0579

AC:

3937

AN:

68032

Other (OTH)

AF:

0.0354

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

306

612

919

1225

1531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0449

Hom.:

552

Bravo

AF:

0.0315

TwinsUK

AF:

0.0556

AC:

206

ALSPAC

AF:

0.0485

AC:

187

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.0508

AC:

437

ExAC

AF:

0.0435

AC:

5281

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0469

EpiControl

AF:

0.0448

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17000706) -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro272Ser in exon 10 of DTNBP1: This variant is not expected to have clinical significance because it has been identified in 5% (437/8600) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs17470454). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;.;T;.;.

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.73

T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.;.;.

PhyloP100

4.2

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.3

N;D;.;.;D

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;.;.;T

Sift4G

Benign

0.11

T;T;T;T;.

Polyphen

0.14

B;.;.;.;.

Vest4

0.099

MPC

0.13

ClinPred

0.019

GERP RS

3.6

Varity_R

0.034

gMVP

0.23

Mutation Taster

=94/6

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