rs11757499

Positions:

• chr6-15599499-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.489-6418A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,164 control chromosomes in the GnomAD database, including 1,470 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 0.12 (1470 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.489-6418A>C		intron_variant		ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.489-6418A>C		intron_variant		1	NM_032122.5	ENSP00000341680	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18894 AN: 152046 Hom.: 1472 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.124 AC: 18912 AN: 152164 Hom.: 1470 Cov.: 32 AF XY: 0.122 AC XY: 9112 AN XY: 74390

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0943 Hom.: 110

Bravo AF: 0.135

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs11757499; hg19: chr6-15599730;