rs12527121

chr6-15545982-C-T

Variant summary

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

The NM_032122.5(DTNBP1):c.512-12587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 435,560 control chromosomes in the GnomAD database, including 1,334 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 0.062 (433 hom., cov: 31)
  • Exomes 𝑓: 0.071 (901 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.512-12587G>A		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-12587G>A		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9445 AN: 151752 Hom.: 432 Cov.: 31

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0570

GnomAD4 exome AF: 0.0712 AC: 20210 AN: 283708 Hom.: 901 AF XY: 0.0674 AC XY: 11023 AN XY: 163502

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0327

Gnomad4 EAS exome AF: 0.000658

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0805

Gnomad4 OTH exome AF: 0.0666

GnomAD4 genome AF: 0.0622 AC: 9450 AN: 151852 Hom.: 433 Cov.: 31 AF XY: 0.0653 AC XY: 4845 AN XY: 74184

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0748 Hom.: 677

Bravo AF: 0.0565

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.56

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: rs12527121; hg19: chr6-15546213;