rs6903266

chr6-15596761-T-C

Variant summary

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

The NM_032122.5(DTNBP1):c.489-3680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,198 control chromosomes in the GnomAD database, including 3,632 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 0.20 (3632 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.489-3680A>G		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-3680A>G		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31175 AN: 152080 Hom.: 3628 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.205 AC: 31189 AN: 152198 Hom.: 3632 Cov.: 32 AF XY: 0.197 AC XY: 14676 AN XY: 74420

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.207

Alfa AF: 0.243 Hom.: 944

Bravo AF: 0.205

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6903266; hg19: chr6-15596992;