rs9358063

Variant names:

• chr6-15564800-T-C
• rs9358063
• NM_032122.5:c.511+28259A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-15564800-T-C
• chr6-15564800-T-G

Variant summary

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

The NM_032122.5(DTNBP1):​c.511+28259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,068 control chromosomes in the GnomAD database, including 20,108 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 0.50 (20108 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• 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), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	NM_032122.5	MANE Select	c.511+28259A>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.460+28259A>G		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.406+28259A>G		intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.511+28259A>G		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.406+28259A>G		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.511+28259A>G		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76037 AN: 151950 Hom.: 20098 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.500 AC: 76091 AN: 152068 Hom.: 20108 Cov.: 33 AF XY: 0.512 AC XY: 38030 AN XY: 74336

African (AFR) AF: 0.362 AC: 15028 AN: 41474

American (AMR) AF: 0.504 AC: 7704 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4491 AN: 5184

South Asian (SAS) AF: 0.676 AC: 3256 AN: 4820

European-Finnish (FIN) AF: 0.649 AC: 6854 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35701 AN: 67950

Other (OTH) AF: 0.473 AC: 1000 AN: 2114

Alfa AF: 0.502 Hom.: 23942

Bravo AF: 0.482

Asia WGS AF: 0.741 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.93
PhyloP100		-0.48
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: rs9358063; hg19: chr6-15565031;