rs2056942

Positions:

• chr6-15542067-A-C
• chr6-15542067-A-G
• chr6-15542067-A-T

Variant summary

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

The ENST00000344537.10(DTNBP1):​c.512-8672T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,042 control chromosomes in the GnomAD database, including 51,851 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 0.82 (51851 hom., cov: 32)
• Consequence: DTNBP1 ENST00000344537.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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=-0.87).
• 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.512-8672T>G		intron_variant		ENST00000344537.10	NP_115498.2
LOC105374947	XR_007059475.1	n.10584A>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-8672T>G		intron_variant		1	NM_032122.5	ENSP00000341680	P1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 124973 AN: 151924 Hom.: 51795 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.837

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.823 AC: 125085 AN: 152042 Hom.: 51851 Cov.: 32 AF XY: 0.830 AC XY: 61702 AN XY: 74338

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.822

Alfa AF: 0.731 Hom.: 2172

Bravo AF: 0.823

Asia WGS AF: 0.951 AC: 3302 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.83

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: rs2056942; hg19: chr6-15542298;