rs909706

chr6-15660640-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.56+2174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 953,832 control chromosomes in the GnomAD database, including 194,169 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 0.66 (33775 hom., cov: 31)
  • Exomes 𝑓: 0.63 (160394 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.56+2174A>G		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.56+2174A>G		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100052 AN: 151924 Hom.: 33727 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.630 AC: 504740 AN: 801790 Hom.: 160394 AF XY: 0.626 AC XY: 252384 AN XY: 403132

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.659 AC: 100155 AN: 152042 Hom.: 33775 Cov.: 31 AF XY: 0.649 AC XY: 48258 AN XY: 74304

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.679

Alfa AF: 0.660 Hom.: 6342

Bravo AF: 0.669

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.3
Dann	Benign	0.71

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: rs909706; hg19: chr6-15660871;