rs12199640

Variant names:

• chr6-15598649-C-T
• rs12199640
• NM_032122.5:c.489-5568G>A

Variant summary

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

The NM_032122.5(DTNBP1):​c.489-5568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 131,872 control chromosomes in the GnomAD database, including 275 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 0.044 (275 hom., cov: 30)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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.489-5568G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.438-5568G>A		intron	N/A	NP_001258597.1
	DTNBP1	NM_001271669.2		c.384-5568G>A		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.489-5568G>A		intron	N/A	ENSP00000341680.6
	DTNBP1	ENST00000622898.4	TSL:1	c.384-5568G>A		intron	N/A	ENSP00000481997.1
	DTNBP1	ENST00000338950.9	TSL:1	c.489-5568G>A		intron	N/A	ENSP00000344718.5

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 5776 AN: 131810 Hom.: 276 Cov.: 30

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00452

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.0506

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0372

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0530

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

GnomAD4 genome AF: 0.0438 AC: 5780 AN: 131872 Hom.: 275 Cov.: 30 AF XY: 0.0476 AC XY: 2962 AN XY: 62164

African (AFR) AF: 0.0132 AC: 458 AN: 34720

American (AMR) AF: 0.0397 AC: 426 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.0506 AC: 169 AN: 3340

East Asian (EAS) AF: 0.280 AC: 1245 AN: 4454

South Asian (SAS) AF: 0.138 AC: 567 AN: 4116

European-Finnish (FIN) AF: 0.0241 AC: 164 AN: 6798

Middle Eastern (MID) AF: 0.0398 AC: 9 AN: 226

European-Non Finnish (NFE) AF: 0.0407 AC: 2636 AN: 64770

Other (OTH) AF: 0.0553 AC: 102 AN: 1844

Alfa AF: 0.0434 Hom.: 630

Bravo AF: 0.0368

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.42
PhyloP100		-0.47
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: rs12199640; hg19: chr6-15598880;