rs148092520

chr6-15627422-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032122.5(DTNBP1):c.276A>G(p.Thr92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,038 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: DTNBP1 NM_032122.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-15627422-T-C is Benign according to our data. Variant chr6-15627422-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 355974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.276A>G	p.Thr92=	synonymous_variant	5/10	ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.276A>G	p.Thr92=	synonymous_variant	5/10	1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 152176 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00206 AC: 516 AN: 250856 Hom.: 14 AF XY: 0.00213 AC XY: 289 AN XY: 135556

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.0405

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000618

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00111 AC: 1625 AN: 1461744 Hom.: 31 Cov.: 32 AF XY: 0.00112 AC XY: 812 AN XY: 727170

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152294 Hom.: 2 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74470

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00367 Hom.: 9

Bravo AF: 0.00143

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.000948

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

Genetic Services Laboratory, University of Chicago

Jan 07, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.83
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs148092520; hg19: chr6-15627653;