rs2619520

Variant names:

• chr6-15655924-C-A
• rs2619520
• NM_032122.5:c.57-3784G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-15655924-C-A
• chr6-15655924-C-G
• chr6-15655924-C-T

Variant summary

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

The NM_032122.5(DTNBP1):​c.57-3784G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,240 control chromosomes in the GnomAD database, including 63,103 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 0.91 (63103 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.57-3784G>T		intron_variant	Intron 1 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.57-3784G>T		intron_variant	Intron 1 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138397 AN: 152122 Hom.: 63054 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.910 AC: 138500 AN: 152240 Hom.: 63103 Cov.: 32 AF XY: 0.910 AC XY: 67737 AN XY: 74438

African (AFR) AF: 0.957 AC: 39752 AN: 41542

American (AMR) AF: 0.889 AC: 13595 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3309 AN: 3468

East Asian (EAS) AF: 0.808 AC: 4185 AN: 5182

South Asian (SAS) AF: 0.872 AC: 4208 AN: 4824

European-Finnish (FIN) AF: 0.913 AC: 9672 AN: 10588

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.893 AC: 60734 AN: 68024

Other (OTH) AF: 0.909 AC: 1920 AN: 2112

Alfa AF: 0.901 Hom.: 75004

Bravo AF: 0.909

Asia WGS AF: 0.832 AC: 2891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		0.21
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: rs2619520; hg19: chr6-15656155;