rs16876575

Variant names:

• chr6-15524926-C-T
• rs16876575
• NM_032122.5:c.668-257G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032122.5(DTNBP1):​c.668-257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,300 control chromosomes in the GnomAD database, including 1,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1590 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-15524926-C-T is Benign according to our data. Variant chr6-15524926-C-T is described in ClinVar as Benign. ClinVar VariationId is 1270549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.668-257G>A		intron_variant	Intron 8 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.668-257G>A		intron_variant	Intron 8 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20972 AN: 152182 Hom.: 1592 Cov.: 33

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.138 AC: 20980 AN: 152300 Hom.: 1590 Cov.: 33 AF XY: 0.141 AC XY: 10474 AN XY: 74464

African (AFR) AF: 0.0839 AC: 3487 AN: 41570

American (AMR) AF: 0.166 AC: 2536 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1392 AN: 5182

South Asian (SAS) AF: 0.175 AC: 845 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1483 AN: 10614

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9841 AN: 68022

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.152 Hom.: 2770

Bravo AF: 0.136

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.56
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16876575; hg19: chr6-15525157;