6-15642675-G-T

Variant names:

• chr6-15642675-G-T
• rs2619553
• NM_032122.5:c.162-4871C>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.162-4871C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,192 control chromosomes in the GnomAD database, including 63,005 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 0.91 (63005 hom., cov: 31)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 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.162-4871C>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.111-4871C>A		intron	N/A	NP_001258597.1
	DTNBP1	NM_001271669.2		c.57-4871C>A		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.162-4871C>A		intron	N/A	ENSP00000341680.6
	DTNBP1	ENST00000622898.4	TSL:1	c.57-4871C>A		intron	N/A	ENSP00000481997.1
	DTNBP1	ENST00000338950.9	TSL:1	c.162-4871C>A		intron	N/A	ENSP00000344718.5

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138264 AN: 152074 Hom.: 62957 Cov.: 31

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.909 AC: 138366 AN: 152192 Hom.: 63005 Cov.: 31 AF XY: 0.909 AC XY: 67674 AN XY: 74414

African (AFR) AF: 0.957 AC: 39740 AN: 41542

American (AMR) AF: 0.888 AC: 13564 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3313 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4137 AN: 5164

South Asian (SAS) AF: 0.872 AC: 4202 AN: 4820

European-Finnish (FIN) AF: 0.913 AC: 9673 AN: 10594

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60692 AN: 68004

Other (OTH) AF: 0.907 AC: 1920 AN: 2116

Alfa AF: 0.898 Hom.: 7166

Bravo AF: 0.909

Asia WGS AF: 0.829 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.37
PhyloP100		-0.67
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: rs2619553; hg19: chr6-15642906;