rs16876738

chr6-15627322-C-Gchr6-15627322-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032122.5(DTNBP1):c.355+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,610,846 control chromosomes in the GnomAD database, including 21,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1866 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19527 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0400

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-15627322-C-G is Benign according to our data. Variant chr6-15627322-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.355+21G>C		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.355+21G>C		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22461 AN: 152010 Hom.: 1866 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.170 AC: 42417 AN: 249564 Hom.: 4049 AF XY: 0.172 AC XY: 23261 AN XY: 135014

Gnomad AFR exome AF: 0.0875

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.302

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.159 AC: 231800 AN: 1458718 Hom.: 19527 Cov.: 32 AF XY: 0.161 AC XY: 116865 AN XY: 725828

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.148 AC: 22474 AN: 152128 Hom.: 1866 Cov.: 32 AF XY: 0.150 AC XY: 11182 AN XY: 74342

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.190

Alfa AF: 0.126 Hom.: 328

Bravo AF: 0.146

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16876738; hg19: chr6-15627553; COSMIC: COSV59038663;