6-15615268-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 3P and 12B. PM2PP3BP6_Very_StrongBS1

The NM_032122.5(DTNBP1):​c.487A>C​(p.Arg163Arg) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000245 in 1,614,172 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

DTNBP1
NM_032122.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.9822
2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
Variant 6-15615268-T-G is Benign according to our data. Variant chr6-15615268-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000643 (98/152328) while in subpopulation AFR AF= 0.00166 (69/41584). AF 95% confidence interval is 0.00134. There are 1 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DTNBP1NM_032122.5 linkc.487A>C p.Arg163Arg splice_region_variant, synonymous_variant Exon 6 of 10 ENST00000344537.10 NP_115498.2 Q96EV8-1A0A0S2Z5U8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DTNBP1ENST00000344537.10 linkc.487A>C p.Arg163Arg splice_region_variant, synonymous_variant Exon 6 of 10 1 NM_032122.5 ENSP00000341680.6 Q96EV8-1

Frequencies

GnomAD3 genomes
AF:
0.000624
AC:
95
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00159
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00663
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000406
AC:
102
AN:
251432
Hom.:
0
AF XY:
0.000361
AC XY:
49
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00154
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00605
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000203
AC:
297
AN:
1461844
Hom.:
0
Cov.:
31
AF XY:
0.000194
AC XY:
141
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00182
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00585
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.000629
GnomAD4 genome
AF:
0.000643
AC:
98
AN:
152328
Hom.:
1
Cov.:
32
AF XY:
0.000537
AC XY:
40
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00663
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000394
Hom.:
0
Bravo
AF:
0.000657
Asia WGS
AF:
0.00115
AC:
4
AN:
3476
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 16, 2020
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
Dec 20, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
CADD
Benign
19
DANN
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.98
dbscSNV1_RF
Pathogenic
0.84
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.

Other links and lift over

dbSNP: rs146546977; hg19: chr6-15615499; API