rs12524251

Variant names:

• chr6-15585901-A-G
• rs12524251
• NM_032122.5:c.511+7158T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+7158T>C		intron_variant	Intron 7 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+7158T>C		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

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

African (AFR) AF: 0.0820 AC: 2311 AN: 28192

American (AMR) AF: 0.156 AC: 3374 AN: 21612

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 5104 AN: 20024

East Asian (EAS) AF: 0.272 AC: 9320 AN: 34236

South Asian (SAS) AF: 0.169 AC: 9924 AN: 58682

European-Finnish (FIN) AF: 0.137 AC: 4052 AN: 29514

Middle Eastern (MID) AF: 0.260 AC: 1209 AN: 4642

European-Non Finnish (NFE) AF: 0.138 AC: 141094 AN: 1021248

Other (OTH) AF: 0.164 AC: 8642 AN: 52714

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

African (AFR) AF: 0.0819 AC: 3403 AN: 41566

American (AMR) AF: 0.159 AC: 2433 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1558 AN: 5170

South Asian (SAS) AF: 0.182 AC: 877 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1534 AN: 10600

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9799 AN: 68022

Other (OTH) AF: 0.176 AC: 372 AN: 2112

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
PhyloP100		1.7
PromoterAI		-0.013	Neutral
Mutation Taster		=299/1	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: rs12524251; hg19: chr6-15586132; COSMIC: COSV59039099;