rs4712253

Variant names:

• chr6-15526186-C-T
• rs4712253
• NM_032122.5:c.668-1517G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.668-1517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,966 control chromosomes in the GnomAD database, including 13,042 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13042 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 8 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

LOC105374947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 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.668-1517G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.617-1517G>A		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.563-1517G>A		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.668-1517G>A		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.563-1517G>A		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.668-1517G>A		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62701 AN: 151848 Hom.: 13024 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62748 AN: 151966 Hom.: 13042 Cov.: 32 AF XY: 0.413 AC XY: 30656 AN XY: 74290

African (AFR) AF: 0.408 AC: 16916 AN: 41412

American (AMR) AF: 0.398 AC: 6083 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1399 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2438 AN: 5174

South Asian (SAS) AF: 0.465 AC: 2244 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4135 AN: 10538

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28171 AN: 67962

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.414 Hom.: 21913

Bravo AF: 0.409

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		-0.99
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: rs4712253; hg19: chr6-15526417;