NM_032122.5:c.511+50A>G

Variant names:

• chr6-15593009-T-C
• rs7758659
• NM_032122.5:c.511+50A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032122.5(DTNBP1):​c.511+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,520,494 control chromosomes in the GnomAD database, including 472,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50233 hom., cov: 30)
  • Exomes 𝑓: 0.78 (421985 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.131
• Publications: 11 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), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-15593009-T-C is Benign according to our data. Variant chr6-15593009-T-C is described in ClinVar as Benign. ClinVar VariationId is 262012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	NM_032122.5	MANE Select	c.511+50A>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.460+50A>G		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.406+50A>G		intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.511+50A>G		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.406+50A>G		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.511+50A>G		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123058 AN: 151848 Hom.: 50184 Cov.: 30

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.800

GnomAD2 exomes AF: 0.824 AC: 159122 AN: 193010 AF XY: 0.823

Gnomad AFR exome AF: 0.865

Gnomad AMR exome AF: 0.873

Gnomad ASJ exome AF: 0.740

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.756

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.783 AC: 1071071 AN: 1368528 Hom.: 421985 Cov.: 21 AF XY: 0.785 AC XY: 534037 AN XY: 679898

African (AFR) AF: 0.869 AC: 26343 AN: 30328

American (AMR) AF: 0.865 AC: 31757 AN: 36716

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 18239 AN: 24438

East Asian (EAS) AF: 1.00 AC: 38548 AN: 38566

South Asian (SAS) AF: 0.901 AC: 68807 AN: 76334

European-Finnish (FIN) AF: 0.831 AC: 42829 AN: 51510

Middle Eastern (MID) AF: 0.830 AC: 4548 AN: 5480

European-Non Finnish (NFE) AF: 0.758 AC: 795021 AN: 1048502

Other (OTH) AF: 0.794 AC: 44979 AN: 56654

GnomAD4 genome AF: 0.810 AC: 123162 AN: 151966 Hom.: 50233 Cov.: 30 AF XY: 0.818 AC XY: 60767 AN XY: 74278

African (AFR) AF: 0.863 AC: 35745 AN: 41438

American (AMR) AF: 0.826 AC: 12610 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2590 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5184

South Asian (SAS) AF: 0.906 AC: 4368 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8843 AN: 10530

Middle Eastern (MID) AF: 0.817 AC: 237 AN: 290

European-Non Finnish (NFE) AF: 0.755 AC: 51282 AN: 67952

Other (OTH) AF: 0.804 AC: 1697 AN: 2112

Alfa AF: 0.775 Hom.: 17276

Bravo AF: 0.808

Asia WGS AF: 0.949 AC: 3297 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		-0.13
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: rs7758659; hg19: chr6-15593240;