6-15525766-A-G

Variant names:

• chr6-15525766-A-G
• rs6937379
• NM_032122.5:c.668-1097T>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.668-1097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,172 control chromosomes in the GnomAD database, including 51,012 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 (51012 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 4 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 (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.668-1097T>C		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.668-1097T>C		intron_variant	Intron 8 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124078 AN: 152054 Hom.: 50970 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.816 AC: 124174 AN: 152172 Hom.: 51012 Cov.: 32 AF XY: 0.823 AC XY: 61264 AN XY: 74396

African (AFR) AF: 0.874 AC: 36290 AN: 41510

American (AMR) AF: 0.831 AC: 12713 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2600 AN: 3466

East Asian (EAS) AF: 0.997 AC: 5163 AN: 5176

South Asian (SAS) AF: 0.906 AC: 4366 AN: 4820

European-Finnish (FIN) AF: 0.842 AC: 8924 AN: 10604

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51554 AN: 67982

Other (OTH) AF: 0.810 AC: 1709 AN: 2110

Alfa AF: 0.777 Hom.: 59942

Bravo AF: 0.815

Asia WGS AF: 0.950 AC: 3305 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	0.055
DANN	Benign	0.20
PhyloP100		-2.9
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: rs6937379; hg19: chr6-15525997;