rs9464796

Positions:

• chr6-15549533-G-A
• chr6-15549533-G-C

Variant summary

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

The NM_032122.5(DTNBP1):​c.512-16138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 145,160 control chromosomes in the GnomAD database, including 47,284 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 0.80 (47284 hom., cov: 22)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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]

LOC124901267 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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	UniProt
DTNBP1	NM_032122.5	c.512-16138C>T		intron_variant		ENST00000344537.10
LOC124901267	XR_007059478.1	n.3464G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-16138C>T		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 116778 AN: 145084 Hom.: 47254 Cov.: 22

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.805 AC: 116845 AN: 145160 Hom.: 47284 Cov.: 22 AF XY: 0.814 AC XY: 57106 AN XY: 70194

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.800

Alfa AF: 0.772 Hom.: 5347

Bravo AF: 0.802

Asia WGS AF: 0.948 AC: 3295 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.42

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: rs9464796; hg19: chr6-15549764;