rs4236167

chr6-15533720-C-T

Variant summary

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

The NM_032122.5(DTNBP1):c.512-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 503,590 control chromosomes in the GnomAD database, including 60,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15894 hom., cov: 33)
  • Exomes 𝑓: 0.50 (44821 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13

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]

LOC105374947 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-15533720-C-T is Benign according to our data. Variant chr6-15533720-C-T is described in ClinVar as [Benign]. Clinvar id is 1225208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.512-325G>A		intron_variant		ENST00000344537.10
LOC105374947	XR_007059475.1	n.6597C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-325G>A		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67622 AN: 152018 Hom.: 15887 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.498 AC: 174995 AN: 351454 Hom.: 44821 AF XY: 0.502 AC XY: 98764 AN XY: 196616

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.445 AC: 67655 AN: 152136 Hom.: 15894 Cov.: 33 AF XY: 0.455 AC XY: 33816 AN XY: 74360

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.411

Alfa AF: 0.471 Hom.: 10259

Bravo AF: 0.427

Asia WGS AF: 0.578 AC: 2006 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	-0.92
Cadd	Benign	0.24
Dann	Benign	0.63

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: rs4236167; hg19: chr6-15533951;