Genetic Variant NM_032122.5:c.512-12587G>A (chr6-15545982-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032122.5(DTNBP1):c.512-12587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 435,560 control chromosomes in the GnomAD database, including 1,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.062 ( 433 hom., cov: 31)

Exomes 𝑓: 0.071 ( 901 hom. )

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

Publications

3 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:

ENSG00000287626 (HGNC:58090):

ENSG00000287626 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.512-12587G>A		intron_variant	Intron 7 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.512-12587G>A		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.0622

AC:

9445

AN:

151752

Hom.:

432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0912

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0388

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.0570

GnomAD4 exome

AF:

0.0712

AC:

20210

AN:

283708

Hom.:

901

AF XY:

0.0674

AC XY:

11023

AN XY:

163502

show subpopulations

African (AFR)

AF:

0.0110

AC:

AN:

6716

American (AMR)

AF:

0.118

AC:

2533

AN:

21444

Ashkenazi Jewish (ASJ)

AF:

0.0327

AC:

317

AN:

9686

East Asian (EAS)

AF:

0.000658

AC:

AN:

9122

South Asian (SAS)

AF:

0.0435

AC:

2493

AN:

57264

European-Finnish (FIN)

AF:

0.138

AC:

1629

AN:

11818

Middle Eastern (MID)

AF:

0.0211

AC:

AN:

2606

European-Non Finnish (NFE)

AF:

0.0805

AC:

12235

AN:

152016

Other (OTH)

AF:

0.0666

AC:

868

AN:

13036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

821

1643

2464

3286

4107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0622

AC:

9450

AN:

151852

Hom.:

433

Cov.:

AF XY:

0.0653

AC XY:

4845

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.0148

AC:

613

AN:

41408

American (AMR)

AF:

0.0914

AC:

1394

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5170

South Asian (SAS)

AF:

0.0391

AC:

188

AN:

4806

European-Finnish (FIN)

AF:

0.145

AC:

1513

AN:

10456

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0803

AC:

5456

AN:

67986

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0731

Hom.:

813

Bravo

AF:

0.0565

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.56

PhyloP100

-0.28

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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NM_032122.5:c.512-12587G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over