rs2743550

Variant names:

• chr6-15582176-C-A
• rs2743550
• NM_032122.5:c.511+10883G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-15582176-C-A
• chr6-15582176-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.511+10883G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,088 control chromosomes in the GnomAD database, including 2,695 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 0.15 (2695 hom., cov: 31)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+10883G>T		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+10883G>T		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23450 AN: 151970 Hom.: 2694 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.154 AC: 23484 AN: 152088 Hom.: 2695 Cov.: 31 AF XY: 0.152 AC XY: 11270 AN XY: 74358

African (AFR) AF: 0.317 AC: 13144 AN: 41462

American (AMR) AF: 0.149 AC: 2281 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 323 AN: 3462

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5166

South Asian (SAS) AF: 0.117 AC: 563 AN: 4818

European-Finnish (FIN) AF: 0.0543 AC: 575 AN: 10588

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5772 AN: 67994

Other (OTH) AF: 0.146 AC: 308 AN: 2108

Alfa AF: 0.121 Hom.: 236

Bravo AF: 0.169

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.83
PhyloP100		-0.57
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: rs2743550; hg19: chr6-15582407;