6-15611596-T-C

Variant names:

• chr6-15611596-T-C
• rs9476864
• NM_032122.5:c.488+3671A>G

Variant summary

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

The NM_032122.5(DTNBP1):​c.488+3671A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,106 control chromosomes in the GnomAD database, including 24,232 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 (24232 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 1 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.488+3671A>G		intron_variant	Intron 6 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.488+3671A>G		intron_variant	Intron 6 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84665 AN: 151988 Hom.: 24214 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.557 AC: 84731 AN: 152106 Hom.: 24232 Cov.: 32 AF XY: 0.548 AC XY: 40744 AN XY: 74380

African (AFR) AF: 0.664 AC: 27520 AN: 41468

American (AMR) AF: 0.536 AC: 8194 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1993 AN: 5176

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4822

European-Finnish (FIN) AF: 0.403 AC: 4258 AN: 10574

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36497 AN: 67986

Other (OTH) AF: 0.591 AC: 1245 AN: 2108

Alfa AF: 0.527 Hom.: 2613

Bravo AF: 0.572

Asia WGS AF: 0.422 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-2.3
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: rs9476864; hg19: chr6-15611827;