6-15527081-G-T

Position:

• chr6-15527081-G-T

Variant summary

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

The NM_032122.5(DTNBP1):​c.668-2412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,148 control chromosomes in the GnomAD database, including 1,529 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 0.13 (1529 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.668-2412C>A		intron_variant		ENST00000344537.10
LOC105374947	XR_007059475.1	n.748G>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.668-2412C>A		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19037 AN: 152032 Hom.: 1531 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.125 AC: 19061 AN: 152148 Hom.: 1529 Cov.: 33 AF XY: 0.123 AC XY: 9181 AN XY: 74392

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.0951

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0946 Hom.: 111

Bravo AF: 0.137

Asia WGS AF: 0.0960 AC: 332 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.43

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: rs9476836; hg19: chr6-15527312;