rs12199640

Positions:

• chr6-15598649-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000344537.10(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 ENST00000344537.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.489-5568G>A		intron_variant		ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-5568G>A		intron_variant		1	NM_032122.5	ENSP00000341680	P1

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

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.0506

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0427 Hom.: 194

Bravo AF: 0.0368

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs12199640; hg19: chr6-15598880;