6-15593088-GAAAAA-GAAAAAAA

Variant names:

• chr6-15593088-G-GAA
• rs199770715
• NM_032122.5:c.489-9_489-8dupTT

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.489-9_489-8dupTT variant causes a splice region, 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, 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 rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.489-9_489-8dupTT		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-8_489-7insTT		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_032122.5	ENSP00000341680.6

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

Nov 07, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;