rs73369534

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.874A>G(p.Arg292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,614,228 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 162 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 132 hom. )

Consequence

DTNBP1
NM_032122.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.01

Publications

4 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=0.002054423).

BP6

Variant 6-15523157-T-C is Benign according to our data. Variant chr6-15523157-T-C is described in ClinVar as Benign. ClinVar VariationId is 226620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.874A>G	p.Arg292Gly	missense_variant	Exon 10 of 10	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 link	c.874A>G	p.Arg292Gly	missense_variant	Exon 10 of 10	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3662

AN:

152220

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00994

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00674

AC:

1696

AN:

251490

AF XY:

0.00483

show subpopulations

Gnomad AFR exome

AF:

0.0860

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00255

AC:

3731

AN:

1461890

Hom.:

132

Cov.:

AF XY:

0.00222

AC XY:

1616

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0842

AC:

2820

AN:

33478

American (AMR)

AF:

0.00559

AC:

250

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00444

AC:

116

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000170

AC:

189

AN:

1112012

Other (OTH)

AF:

0.00546

AC:

330

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

242

485

727

970

1212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.0240

AC:

3662

AN:

152338

Hom.:

162

Cov.:

AF XY:

0.0239

AC XY:

1784

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0827

AC:

3438

AN:

41558

American (AMR)

AF:

0.00993

AC:

152

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68040

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

169

337

506

674

843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00920

Hom.:

104

Bravo

AF:

0.0271

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0908

AC:

400

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00829

AC:

1007

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Arg292Gly in exon 10 of DTNBP1: This variant is not expected to have clinical si gnificance because it has been identified in 9.1% (400/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs73369534).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.28

T;.;T;.;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.69

T;T;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

2.0

M;.;.;.;.

PhyloP100

3.0

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-2.7

D;D;.;.;D

REVEL

Benign

0.13

Sift

Benign

0.048

D;T;.;.;T

Sift4G

Benign

0.26

T;T;T;T;.

Vest4

0.22

ClinPred

0.021

GERP RS

2.4

Varity_R

0.12

gMVP

0.077

Mutation Taster

=97/3

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