rs11756738

Variant names:

• chr6-15597930-T-C
• rs11756738
• NM_032122.5:c.489-4849A>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.489-4849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,234 control chromosomes in the GnomAD database, including 3,518 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 0.20 (3518 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• 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), G2P, ClinGen

ENSG00000307291 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 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.489-4849A>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.438-4849A>G		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.384-4849A>G		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.489-4849A>G		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.384-4849A>G		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.489-4849A>G		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30396 AN: 152116 Hom.: 3516 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.200 AC: 30401 AN: 152234 Hom.: 3518 Cov.: 32 AF XY: 0.192 AC XY: 14288 AN XY: 74430

African (AFR) AF: 0.124 AC: 5150 AN: 41548

American (AMR) AF: 0.181 AC: 2767 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5188

South Asian (SAS) AF: 0.0989 AC: 476 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2069 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18230 AN: 68012

Other (OTH) AF: 0.202 AC: 428 AN: 2114

Alfa AF: 0.228 Hom.: 524

Bravo AF: 0.198

Asia WGS AF: 0.0530 AC: 184 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.87
PhyloP100		0.051
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: rs11756738; hg19: chr6-15598161;