6-15527081-G-T

Variant names:

• chr6-15527081-G-T
• rs9476836
• NM_032122.5:c.668-2412C>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.668-2412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,148 control chromosomes in the GnomAD database, including 1,529 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 0.13 (1529 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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

LOC105374947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.668-2412C>A		intron_variant	Intron 8 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.668-2412C>A		intron_variant	Intron 8 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19037 AN: 152032 Hom.: 1531 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.125 AC: 19061 AN: 152148 Hom.: 1529 Cov.: 33 AF XY: 0.123 AC XY: 9181 AN XY: 74392

African (AFR) AF: 0.228 AC: 9459 AN: 41482

American (AMR) AF: 0.134 AC: 2055 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.0749 AC: 388 AN: 5178

South Asian (SAS) AF: 0.0951 AC: 459 AN: 4826

European-Finnish (FIN) AF: 0.0540 AC: 572 AN: 10586

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0809 AC: 5504 AN: 68006

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.100 Hom.: 132

Bravo AF: 0.137

Asia WGS AF: 0.0960 AC: 332 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.056
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: rs9476836; hg19: chr6-15527312;