6-15593088-GAAAAA-GAAAAAAA

Position:

• chr6-15593088-GAAAAA-GAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_032122.5(DTNBP1):​c.489-8_489-7insTT 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 0.00395 in 1,337,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0043 (0 hom.)
• Consequence: DTNBP1 NM_032122.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.127

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-15593088-G-GAA is Benign according to our data. Variant chr6-15593088-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1336309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000854 (116/135882) while in subpopulation AFR AF= 0.00243 (91/37500). AF 95% confidence interval is 0.00202. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.489-8_489-7insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-8_489-7insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.000854 AC: 116 AN: 135848 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000442

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000823

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.000680

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000145

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00430 AC: 5166 AN: 1201812 Hom.: 0 Cov.: 0 AF XY: 0.00442 AC XY: 2649 AN XY: 598690

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00749

Gnomad4 ASJ exome AF: 0.00376

Gnomad4 EAS exome AF: 0.0108

Gnomad4 SAS exome AF: 0.00975

Gnomad4 FIN exome AF: 0.00216

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.000854 AC: 116 AN: 135882 Hom.: 0 Cov.: 28 AF XY: 0.000977 AC XY: 64 AN XY: 65514

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.000442

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000827

Gnomad4 SAS AF: 0.000232

Gnomad4 FIN AF: 0.000680

Gnomad4 NFE AF: 0.000145

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 07, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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;