Genetic Variant DTNBP1:c.512-24213T>A (chr6-15557608-A-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.512-24213T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,132 control chromosomes in the GnomAD database, including 52,510 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 0.83 ( 52510 hom., cov: 32)

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

1 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), G2P, ClinGen

DTNBP1 links:

DTNBP1-AS1 (HGNC:58090):

DTNBP1-AS1 links:

Genome browser will be placed here

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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	NM_032122.5	MANE Select	c.512-24213T>A	intron	N/A	NP_115498.2
DTNBP1	NM_001271668.2		c.461-24213T>A	intron	N/A	NP_001258597.1	A6NFV8
DTNBP1	NM_001271669.2		c.407-24213T>A	intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.512-24213T>A	intron	N/A	ENSP00000341680.6	Q96EV8-1
DTNBP1	ENST00000622898.4	TSL:1	c.407-24213T>A	intron	N/A	ENSP00000481997.1	A0A087WYP9
DTNBP1	ENST00000338950.9	TSL:1	c.512-24213T>A	intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125671

AN:

152014

Hom.:

52450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.831

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.907

Gnomad FIN

AF:

0.838

Gnomad MID

AF:

0.821

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.814

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.827

AC:

125787

AN:

152132

Hom.:

52510

Cov.:

AF XY:

0.834

AC XY:

62004

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.920

AC:

38225

AN:

41532

American (AMR)

AF:

0.832

AC:

12716

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.748

AC:

2590

AN:

3464

East Asian (EAS)

AF:

0.998

AC:

5166

AN:

5176

South Asian (SAS)

AF:

0.905

AC:

4362

AN:

4818

European-Finnish (FIN)

AF:

0.838

AC:

8856

AN:

10572

Middle Eastern (MID)

AF:

0.822

AC:

240

AN:

292

European-Non Finnish (NFE)

AF:

0.755

AC:

51285

AN:

67966

Other (OTH)

AF:

0.817

AC:

1727

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1114

2228

3341

4455

5569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.795

Hom.:

5994

Bravo

AF:

0.828

Asia WGS

AF:

0.951

AC:

3284

AN:

3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.0

(source)

DANN

Benign

0.46

PhyloP100

-1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over