rs12525702

chr6-15627540-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032122.5(DTNBP1):c.223-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,602,088 control chromosomes in the GnomAD database, including 9,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (846 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9081 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-15627540-C-T is Benign according to our data. Variant chr6-15627540-C-T is described in ClinVar as [Benign]. Clinvar id is 1282033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.223-65G>A		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.223-65G>A		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14160 AN: 151982 Hom.: 846 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.107 AC: 155824 AN: 1449988 Hom.: 9081 AF XY: 0.107 AC XY: 77480 AN XY: 721160

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.0616

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.0931 AC: 14161 AN: 152100 Hom.: 846 Cov.: 32 AF XY: 0.0944 AC XY: 7017 AN XY: 74340

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.126

Alfa AF: 0.108 Hom.: 499

Bravo AF: 0.0901

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.5
Dann	Benign	0.78

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: rs12525702; hg19: chr6-15627771;