6-15573119-A-T

Variant names:

• chr6-15573119-A-T
• rs760665
• NM_032122.5:c.511+19940T>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.511+19940T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,254 control chromosomes in the GnomAD database, including 52,489 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 0.83 (52489 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+19940T>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.511+19940T>A		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125889 AN: 152136 Hom.: 52433 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.828 AC: 126001 AN: 152254 Hom.: 52489 Cov.: 32 AF XY: 0.834 AC XY: 62083 AN XY: 74444

African (AFR) AF: 0.894 AC: 37121 AN: 41536

American (AMR) AF: 0.841 AC: 12875 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2656 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5175 AN: 5184

South Asian (SAS) AF: 0.905 AC: 4367 AN: 4824

European-Finnish (FIN) AF: 0.842 AC: 8927 AN: 10606

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52269 AN: 68008

Other (OTH) AF: 0.826 AC: 1747 AN: 2116

Alfa AF: 0.799 Hom.: 6061

Bravo AF: 0.828

Asia WGS AF: 0.951 AC: 3307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.45
PhyloP100		-1.0
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: rs760665; hg19: chr6-15573350;