6-15557608-A-T

Position:

• chr6-15557608-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.512-24213T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,132 control chromosomes in the GnomAD database, including 52,510 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 0.83 (52510 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

ENSG00000287626 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.512-24213T>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.512-24213T>A		intron_variant		1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125671 AN: 152014 Hom.: 52450 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.821

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.827 AC: 125787 AN: 152132 Hom.: 52510 Cov.: 32 AF XY: 0.834 AC XY: 62004 AN XY: 74374

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.817

Alfa AF: 0.795 Hom.: 5994

Bravo AF: 0.828

Asia WGS AF: 0.951 AC: 3284 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.46

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: rs6918834; hg19: chr6-15557839;