NM_032122.5:c.512-107G>A

Variant names:

• chr6-15533502-C-T
• rs11753919
• NM_032122.5:c.512-107G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032122.5(DTNBP1):​c.512-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,569,016 control chromosomes in the GnomAD database, including 10,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2613 hom., cov: 32)
  • Exomes 𝑓: 0.097 (8068 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291
• Publications: 4 publications found

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]

DTNBP1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

LOC105374947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-15533502-C-T is Benign according to our data. Variant chr6-15533502-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.512-107G>A		intron_variant	Intron 7 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.512-107G>A		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23198 AN: 152046 Hom.: 2612 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.0970 AC: 137454 AN: 1416852 Hom.: 8068 Cov.: 25 AF XY: 0.0964 AC XY: 68194 AN XY: 707246

African (AFR) AF: 0.331 AC: 10795 AN: 32602

American (AMR) AF: 0.144 AC: 6415 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 2360 AN: 25850

East Asian (EAS) AF: 0.0713 AC: 2808 AN: 39404

South Asian (SAS) AF: 0.115 AC: 9743 AN: 84794

European-Finnish (FIN) AF: 0.0511 AC: 2617 AN: 51188

Middle Eastern (MID) AF: 0.148 AC: 837 AN: 5664

European-Non Finnish (NFE) AF: 0.0890 AC: 95635 AN: 1073948

Other (OTH) AF: 0.106 AC: 6244 AN: 58838

GnomAD4 genome AF: 0.153 AC: 23227 AN: 152164 Hom.: 2613 Cov.: 32 AF XY: 0.150 AC XY: 11174 AN XY: 74416

African (AFR) AF: 0.311 AC: 12907 AN: 41460

American (AMR) AF: 0.148 AC: 2265 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.0768 AC: 397 AN: 5170

South Asian (SAS) AF: 0.117 AC: 565 AN: 4822

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10616

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5759 AN: 68016

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.101 Hom.: 569

Bravo AF: 0.167

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11753919; hg19: chr6-15533733; COSMIC: COSV59044020;