rs742106

Positions:

• chr6-15524249-G-A
• chr6-15524249-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000344537.10(DTNBP1):​c.811+277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,583,464 control chromosomes in the GnomAD database, including 114,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9198 hom., cov: 32)
  • Exomes 𝑓: 0.38 (105070 hom.)
• Consequence: DTNBP1 ENST00000344537.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-15524249-G-A is Benign according to our data. Variant chr6-15524249-G-A is described in ClinVar as [Benign]. Clinvar id is 1257273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.811+277C>T		intron_variant		ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.811+277C>T		intron_variant		1	NM_032122.5	ENSP00000341680	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50076 AN: 151904 Hom.: 9185 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.317

GnomAD3 exomes AF: 0.407 AC: 89690 AN: 220256 Hom.: 19149 AF XY: 0.406 AC XY: 48733 AN XY: 120068

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.562

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.387

GnomAD4 exome AF: 0.378 AC: 541410 AN: 1431442 Hom.: 105070 Cov.: 48 AF XY: 0.381 AC XY: 270772 AN XY: 711082

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.330 AC: 50101 AN: 152022 Hom.: 9198 Cov.: 32 AF XY: 0.340 AC XY: 25244 AN XY: 74298

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.317

Alfa AF: 0.354 Hom.: 13827

Bravo AF: 0.325

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs742106; hg19: chr6-15524480;