rs76349207
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032122.5(DTNBP1):c.662G>A(p.Arg221Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000509 in 1,613,920 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00035 ( 1 hom. )
Consequence
DTNBP1
NM_032122.5 missense
NM_032122.5 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 4.94
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011042416).
BP6
Variant 6-15533245-C-T is Benign according to our data. Variant chr6-15533245-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434963.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 = 0.00199 (303/152256) while in subpopulation AFR AF= 0.00589 (245/41564). AF 95% confidence interval is 0.00529. There are 2 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNBP1 | NM_032122.5 | c.662G>A | p.Arg221Gln | missense_variant | 8/10 | ENST00000344537.10 | NP_115498.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNBP1 | ENST00000344537.10 | c.662G>A | p.Arg221Gln | missense_variant | 8/10 | 1 | NM_032122.5 | ENSP00000341680.6 |
Frequencies
GnomAD3 genomes AF: 0.00199 AC: 302AN: 152138Hom.: 2 Cov.: 31
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GnomAD3 exomes AF: 0.000565 AC: 142AN: 251384Hom.: 1 AF XY: 0.000456 AC XY: 62AN XY: 135876
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GnomAD4 exome AF: 0.000354 AC: 518AN: 1461664Hom.: 1 Cov.: 32 AF XY: 0.000359 AC XY: 261AN XY: 727126
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GnomAD4 genome AF: 0.00199 AC: 303AN: 152256Hom.: 2 Cov.: 31 AF XY: 0.00192 AC XY: 143AN XY: 74434
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 05, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 23, 2016 | - - |
DTNBP1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 16, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;N;N;N
REVEL
Benign
Sift
Benign
T;T;.;.;T;T;T
Sift4G
Benign
T;T;T;T;.;T;.
Polyphen
D;.;.;.;.;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at