rs2743548

chr6-15583593-A-Cchr6-15583593-A-Gchr6-15583593-A-T

Variant summary

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

The NM_032122.5(DTNBP1):c.511+9466T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,242 control chromosomes in the GnomAD database, including 1,468 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 0.12 (1468 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.511+9466T>G		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+9466T>G		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18895 AN: 152124 Hom.: 1469 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0817

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.124 AC: 18914 AN: 152242 Hom.: 1468 Cov.: 32 AF XY: 0.123 AC XY: 9124 AN XY: 74456

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0817

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0941 Hom.: 109

Bravo AF: 0.135

Asia WGS AF: 0.107 AC: 370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
Dann	Benign	0.75

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: rs2743548; hg19: chr6-15583824;