6-15593088-GAAAAA-GAAA

Position:

• chr6-15593088-GAAAAA-GAAA

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The NM_032122.5(DTNBP1):​c.489-9_489-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,300,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0054 (0 hom.)
• Consequence: DTNBP1 NM_032122.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-15593088-GAA-G is Benign according to our data. Variant chr6-15593088-GAA-G is described in Lovd as [Benign]. Variant chr6-15593088-GAA-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0054 (6284/1164186) while in subpopulation AMR AF= 0.0174 (479/27520). AF 95% confidence interval is 0.0161. There are 0 homozygotes in gnomad4_exome. There are 3266 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.489-9_489-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-9_489-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032122.5	ENSP00000341680	P1

Frequencies

GnomAD3 genomes AF: 0.0000736 AC: 10 AN: 135800 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000409

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000806

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00540 AC: 6284 AN: 1164186 Hom.: 0 AF XY: 0.00563 AC XY: 3266 AN XY: 580110

Gnomad4 AFR exome AF: 0.00630

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.00643

Gnomad4 EAS exome AF: 0.00832

Gnomad4 SAS exome AF: 0.00815

Gnomad4 FIN exome AF: 0.00888

Gnomad4 NFE exome AF: 0.00443

Gnomad4 OTH exome AF: 0.00640

GnomAD4 genome AF: 0.0000736 AC: 10 AN: 135832 Hom.: 0 Cov.: 28 AF XY: 0.0000916 AC XY: 6 AN XY: 65486

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000409

Gnomad4 NFE AF: 0.0000806

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199770715; hg19: chr6-15593319;