rs9296979

Variant names:

• chr6-15530553-A-C
• rs9296979
• NM_032122.5:c.667+2687T>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.667+2687T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,108 control chromosomes in the GnomAD database, including 3,059 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 0.16 (3059 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• Publications: 2 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

LOC105374947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.667+2687T>G		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.667+2687T>G		intron_variant	Intron 8 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24468 AN: 151990 Hom.: 3051 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.161 AC: 24520 AN: 152108 Hom.: 3059 Cov.: 33 AF XY: 0.158 AC XY: 11782 AN XY: 74342

African (AFR) AF: 0.343 AC: 14222 AN: 41446

American (AMR) AF: 0.151 AC: 2314 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3472

East Asian (EAS) AF: 0.0779 AC: 403 AN: 5176

South Asian (SAS) AF: 0.117 AC: 561 AN: 4808

European-Finnish (FIN) AF: 0.0540 AC: 572 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5694 AN: 67994

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.108 Hom.: 5122

Bravo AF: 0.177

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.37
PhyloP100		0.23
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: rs9296979; hg19: chr6-15530784;