rs12524251

Positions:

• chr6-15585901-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032122.5(DTNBP1):​c.511+7158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,423,126 control chromosomes in the GnomAD database, including 16,181 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 0.14 (1659 hom., cov: 32)
  • Exomes 𝑓: 0.15 (14522 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.511+7158T>C		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+7158T>C		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21006 AN: 152144 Hom.: 1659 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.146 AC: 185030 AN: 1270864 Hom.: 14522 Cov.: 33 AF XY: 0.147 AC XY: 90945 AN XY: 617318

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.138 AC: 21020 AN: 152262 Hom.: 1659 Cov.: 32 AF XY: 0.141 AC XY: 10531 AN XY: 74434

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.176

Alfa AF: 0.143 Hom.: 210

Bravo AF: 0.135

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.89

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: rs12524251; hg19: chr6-15586132; COSMIC: COSV59039099;