rs17470454

Positions:

chr6-15523217-G-A

Variant summary

Our verdict is Benign. Variant got -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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 [Likely_benign]. Clinvar id is 163299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-15523217-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5 linkuse as main transcript	c.814C>T	p.Pro272Ser	missense_variant, splice_region_variant	10/10	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.814C>T	p.Pro272Ser	missense_variant, splice_region_variant	10/10	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

GnomAD3 exomes

AF:

0.0425

AC:

10675

AN:

251402

Hom.:

402

AF XY:

0.0423

AC XY:

5747

AN XY:

135910

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 SAS exome

AF:

0.00372

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

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00486

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.0557

Gnomad4 OTH exome

AF:

0.0405

GnomAD4 genome

AF:

0.0415

AC:

6328

AN:

152328

Hom.:

201

Cov.:

AF XY:

0.0429

AC XY:

3198

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00943

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0579

Gnomad4 OTH

AF:

0.0354

Alfa

AF:

0.0466

Hom.:

409

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

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 17000706) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 12, 2014	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -

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

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;.;.;.;.

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

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