6-15634011-G-C

Variant names:

• chr6-15634011-G-C
• rs2619550
• NM_032122.5:c.222+3733C>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.222+3733C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,684 control chromosomes in the GnomAD database, including 5,476 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 0.25 (5476 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• 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 = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	NM_032122.5	MANE Select	c.222+3733C>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.171+3733C>G		intron	N/A	NP_001258597.1
	DTNBP1	NM_001271669.2		c.117+3733C>G		intron	N/A	NP_001258598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.222+3733C>G		intron	N/A	ENSP00000341680.6
	DTNBP1	ENST00000622898.4	TSL:1	c.117+3733C>G		intron	N/A	ENSP00000481997.1
	DTNBP1	ENST00000338950.9	TSL:1	c.222+3733C>G		intron	N/A	ENSP00000344718.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38012 AN: 151566 Hom.: 5469 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.251 AC: 38060 AN: 151684 Hom.: 5476 Cov.: 32 AF XY: 0.249 AC XY: 18431 AN XY: 74130

African (AFR) AF: 0.396 AC: 16370 AN: 41296

American (AMR) AF: 0.209 AC: 3196 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3464

East Asian (EAS) AF: 0.0958 AC: 495 AN: 5166

South Asian (SAS) AF: 0.204 AC: 975 AN: 4788

European-Finnish (FIN) AF: 0.215 AC: 2264 AN: 10532

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13455 AN: 67868

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.0987 Hom.: 142

Bravo AF: 0.258

Asia WGS AF: 0.172 AC: 597 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.19
PhyloP100		-0.98
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: rs2619550; hg19: chr6-15634242;