6-15524926-C-T

Position:

• chr6-15524926-C-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.668-257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,300 control chromosomes in the GnomAD database, including 1,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1590 hom., cov: 33)
• Consequence: DTNBP1 ENST00000344537.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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=-0.92).
• BP6: Variant 6-15524926-C-T is Benign according to our data. Variant chr6-15524926-C-T is described in ClinVar as [Benign]. Clinvar id is 1270549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.668-257G>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.668-257G>A		intron_variant		1	NM_032122.5	ENSP00000341680	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20972 AN: 152182 Hom.: 1592 Cov.: 33

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.138 AC: 20980 AN: 152300 Hom.: 1590 Cov.: 33 AF XY: 0.141 AC XY: 10474 AN XY: 74464

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.185

Alfa AF: 0.155 Hom.: 1959

Bravo AF: 0.136

Asia WGS AF: 0.216 AC: 752 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	0.95
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: rs16876575; hg19: chr6-15525157;