rs9476886

Variant names:

• chr6-15661230-C-T
• rs9476886
• NM_032122.5:c.56+1584G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.56+1584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,098 control chromosomes in the GnomAD database, including 8,655 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 0.33 (8655 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.56+1584G>A		intron_variant	Intron 1 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.56+1584G>A		intron_variant	Intron 1 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50071 AN: 151980 Hom.: 8649 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.330 AC: 50118 AN: 152098 Hom.: 8655 Cov.: 32 AF XY: 0.330 AC XY: 24504 AN XY: 74348

African (AFR) AF: 0.430 AC: 17853 AN: 41472

American (AMR) AF: 0.345 AC: 5266 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2043 AN: 5170

South Asian (SAS) AF: 0.337 AC: 1627 AN: 4822

European-Finnish (FIN) AF: 0.225 AC: 2383 AN: 10576

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18358 AN: 67988

Other (OTH) AF: 0.363 AC: 767 AN: 2114

Alfa AF: 0.302 Hom.: 9037

Bravo AF: 0.342

Asia WGS AF: 0.369 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.38
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9476886; hg19: chr6-15661461;