6-15594788-G-C

Variant names:

• chr6-15594788-G-C
• rs6906100
• NM_032122.5:c.489-1707C>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.489-1707C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 151,946 control chromosomes in the GnomAD database, including 51,104 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 0.82 (51104 hom., cov: 29)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	NM_032122.5	MANE Select	c.489-1707C>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.438-1707C>G		intron	N/A	NP_001258597.1
	DTNBP1	NM_001271669.2		c.384-1707C>G		intron	N/A	NP_001258598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.489-1707C>G		intron	N/A	ENSP00000341680.6
	DTNBP1	ENST00000622898.4	TSL:1	c.384-1707C>G		intron	N/A	ENSP00000481997.1
	DTNBP1	ENST00000338950.9	TSL:1	c.489-1707C>G		intron	N/A	ENSP00000344718.5

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124033 AN: 151828 Hom.: 51047 Cov.: 29

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.817 AC: 124146 AN: 151946 Hom.: 51104 Cov.: 29 AF XY: 0.824 AC XY: 61211 AN XY: 74254

African (AFR) AF: 0.886 AC: 36723 AN: 41434

American (AMR) AF: 0.829 AC: 12653 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2590 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5168 AN: 5178

South Asian (SAS) AF: 0.905 AC: 4354 AN: 4810

European-Finnish (FIN) AF: 0.838 AC: 8831 AN: 10532

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51261 AN: 67938

Other (OTH) AF: 0.810 AC: 1707 AN: 2108

Alfa AF: 0.785 Hom.: 5506

Bravo AF: 0.816

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.31
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: rs6906100; hg19: chr6-15595019;