NM_032122.5:c.668-3467G>A

Variant names:

• chr6-15528136-C-T
• rs9296978
• NM_032122.5:c.668-3467G>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.668-3467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,158 control chromosomes in the GnomAD database, including 2,995 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 0.16 (2995 hom., cov: 33)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• 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), G2P, ClinGen

LOC105374947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	NM_032122.5	MANE Select	c.668-3467G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.617-3467G>A		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.563-3467G>A		intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.668-3467G>A		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.563-3467G>A		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.668-3467G>A		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24202 AN: 152040 Hom.: 2987 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.0994

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.159 AC: 24250 AN: 152158 Hom.: 2995 Cov.: 33 AF XY: 0.157 AC XY: 11645 AN XY: 74392

African (AFR) AF: 0.340 AC: 14079 AN: 41466

American (AMR) AF: 0.151 AC: 2303 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.0751 AC: 389 AN: 5182

South Asian (SAS) AF: 0.0993 AC: 479 AN: 4826

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10608

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5683 AN: 68006

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.107 Hom.: 411

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		0.035
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: rs9296978; hg19: chr6-15528367;