Genetic Variant DTNBP1:c.110+17A>C (chr6-15652070-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032122.5(DTNBP1):c.110+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.207

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), G2P, ClinGen

DTNBP1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_032122.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-15652070-T-G is Benign according to our data. Variant chr6-15652070-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 4741582.Status of the report is criteria_provided_single_submitter, 1 stars.

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.110+17A>C	intron	N/A	NP_115498.2
DTNBP1	NM_001271668.2		c.110+17A>C	intron	N/A	NP_001258597.1	A6NFV8
DTNBP1	NM_001271669.2		c.56+10744A>C	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.110+17A>C	intron	N/A	ENSP00000341680.6	Q96EV8-1
DTNBP1	ENST00000622898.4	TSL:1	c.56+10744A>C	intron	N/A	ENSP00000481997.1	A0A087WYP9
DTNBP1	ENST00000338950.9	TSL:1	c.110+17A>C	intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458772

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.00

AC:

AN:

86000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109686

Other (OTH)

AF:

0.00

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.21

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over