rs9296978

chr6-15528136-C-T

Variant summary

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

The NM_032122.5(DTNBP1):c.668-3467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,158 control chromosomes in the GnomAD database, including 2,995 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 0.16 (2995 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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]

LOC105374947 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.668-3467G>A		intron_variant		ENST00000344537.10
LOC105374947	XR_007059475.1	n.1803C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.668-3467G>A		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24202 AN: 152040 Hom.: 2987 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.0994

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.159 AC: 24250 AN: 152158 Hom.: 2995 Cov.: 33 AF XY: 0.157 AC XY: 11645 AN XY: 74392

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.145

Alfa AF: 0.104 Hom.: 365

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.63

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: rs9296978; hg19: chr6-15528367;