rs6909929

Variant names:

• chr6-15604224-A-G
• rs6909929
• NM_032122.5:c.488+11043T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-15604224-A-G
• chr6-15604224-A-T

Variant summary

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

The NM_032122.5(DTNBP1):​c.488+11043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,068 control chromosomes in the GnomAD database, including 34,333 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 0.66 (34333 hom., cov: 31)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.488+11043T>C		intron_variant	Intron 6 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.488+11043T>C		intron_variant	Intron 6 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100513 AN: 151950 Hom.: 34282 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.662 AC: 100618 AN: 152068 Hom.: 34333 Cov.: 31 AF XY: 0.653 AC XY: 48507 AN XY: 74316

African (AFR) AF: 0.821 AC: 34056 AN: 41488

American (AMR) AF: 0.598 AC: 9146 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2060 AN: 5160

South Asian (SAS) AF: 0.527 AC: 2540 AN: 4822

European-Finnish (FIN) AF: 0.530 AC: 5598 AN: 10554

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42607 AN: 67968

Other (OTH) AF: 0.677 AC: 1430 AN: 2112

Alfa AF: 0.472 Hom.: 1057

Bravo AF: 0.673

Asia WGS AF: 0.480 AC: 1673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.10
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: rs6909929; hg19: chr6-15604455;