rs13198195

Variant names:

• chr6-15628592-A-G
• rs13198195
• NM_032122.5:c.223-1117T>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.223-1117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,522 control chromosomes in the GnomAD database, including 3,288 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 0.20 (3288 hom., cov: 29)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.223-1117T>C		intron_variant	Intron 4 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.223-1117T>C		intron_variant	Intron 4 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29733 AN: 151410 Hom.: 3284 Cov.: 29

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00233

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.196 AC: 29751 AN: 151522 Hom.: 3288 Cov.: 29 AF XY: 0.189 AC XY: 14008 AN XY: 74022

African (AFR) AF: 0.142 AC: 5856 AN: 41332

American (AMR) AF: 0.170 AC: 2592 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 854 AN: 3462

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5146

South Asian (SAS) AF: 0.0974 AC: 468 AN: 4804

European-Finnish (FIN) AF: 0.192 AC: 2010 AN: 10446

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17206 AN: 67810

Other (OTH) AF: 0.195 AC: 409 AN: 2100

Alfa AF: 0.219 Hom.: 509

Bravo AF: 0.196

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.9
DANN	Benign	0.52
PhyloP100		1.5
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: rs13198195; hg19: chr6-15628823;