rs9464796

Variant names:

• chr6-15549533-G-A
• rs9464796
• NM_032122.5:c.512-16138C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-15549533-G-A
• chr6-15549533-G-C

Variant summary

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

The NM_032122.5(DTNBP1):​c.512-16138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 145,160 control chromosomes in the GnomAD database, including 47,284 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 0.80 (47284 hom., cov: 22)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• 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

DTNBP1-AS1 (HGNC:58090):

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 (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.512-16138C>T		intron_variant	Intron 7 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-16138C>T		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.805 AC: 116778 AN: 145084 Hom.: 47254 Cov.: 22

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.805 AC: 116845 AN: 145160 Hom.: 47284 Cov.: 22 AF XY: 0.814 AC XY: 57106 AN XY: 70194

African (AFR) AF: 0.860 AC: 33223 AN: 38614

American (AMR) AF: 0.821 AC: 11786 AN: 14356

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2539 AN: 3442

East Asian (EAS) AF: 0.998 AC: 4928 AN: 4938

South Asian (SAS) AF: 0.907 AC: 4181 AN: 4612

European-Finnish (FIN) AF: 0.840 AC: 7481 AN: 8910

Middle Eastern (MID) AF: 0.825 AC: 226 AN: 274

European-Non Finnish (NFE) AF: 0.749 AC: 50241 AN: 67084

Other (OTH) AF: 0.800 AC: 1624 AN: 2030

Alfa AF: 0.772 Hom.: 5347

Bravo AF: 0.802

Asia WGS AF: 0.948 AC: 3295 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.42
PhyloP100		-0.80
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: rs9464796; hg19: chr6-15549764;