Genetic Variant DTNBP1:c.57-1062A>C (chr6-15653202-T-G) – 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.57-1062A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 152,308 control chromosomes in the GnomAD database, including 74,695 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 0.99 ( 74695 hom., cov: 32)

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203

Publications

0 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:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 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
DTNBP1	NM_032122.5	MANE Select	c.57-1062A>C	intron	N/A	NP_115498.2
DTNBP1	NM_001271668.2		c.57-1062A>C	intron	N/A	NP_001258597.1
DTNBP1	NM_001271669.2		c.56+9612A>C	intron	N/A	NP_001258598.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.57-1062A>C	intron	N/A	ENSP00000341680.6
DTNBP1	ENST00000622898.4	TSL:1	c.56+9612A>C	intron	N/A	ENSP00000481997.1
DTNBP1	ENST00000338950.9	TSL:1	c.57-1062A>C	intron	N/A	ENSP00000344718.5

Frequencies

GnomAD3 genomes

AF:

0.990

AC:

150721

AN:

152190

Hom.:

74636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.978

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.993

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

GnomAD4 genome

AF:

0.990

AC:

150839

AN:

152308

Hom.:

74695

Cov.:

AF XY:

0.991

AC XY:

73796

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.997

AC:

41447

AN:

41564

American (AMR)

AF:

0.992

AC:

15177

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3460

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5194

AN:

5194

South Asian (SAS)

AF:

0.999

AC:

4827

AN:

4830

European-Finnish (FIN)

AF:

0.978

AC:

10379

AN:

10610

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.986

AC:

67055

AN:

68028

Other (OTH)

AF:

0.993

AC:

2095

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

146

220

293

366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.990

Hom.:

9402

Bravo

AF:

0.991

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.58

(source)

DANN

Benign

0.36

PhyloP100

-0.20

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