6-15620624-C-G

Variant names:

• chr6-15620624-C-G
• rs2619539
• NM_032122.5:c.356-5225G>C

Variant summary

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

The NM_032122.5(DTNBP1):​c.356-5225G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,154 control chromosomes in the GnomAD database, including 24,810 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 0.56 (24810 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• Publications: 37 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.356-5225G>C		intron_variant	Intron 5 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.356-5225G>C		intron_variant	Intron 5 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85427 AN: 152036 Hom.: 24780 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.562 AC: 85507 AN: 152154 Hom.: 24810 Cov.: 33 AF XY: 0.553 AC XY: 41107 AN XY: 74386

African (AFR) AF: 0.688 AC: 28546 AN: 41510

American (AMR) AF: 0.536 AC: 8190 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2208 AN: 3462

East Asian (EAS) AF: 0.384 AC: 1986 AN: 5174

South Asian (SAS) AF: 0.448 AC: 2162 AN: 4822

European-Finnish (FIN) AF: 0.400 AC: 4229 AN: 10578

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36300 AN: 68002

Other (OTH) AF: 0.592 AC: 1253 AN: 2116

Alfa AF: 0.357 Hom.: 798

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		0.67
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: rs2619539; hg19: chr6-15620855;