rs12527121

Variant names:

• chr6-15545982-C-T
• rs12527121
• NM_032122.5:c.512-12587G>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.512-12587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 435,560 control chromosomes in the GnomAD database, including 1,334 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 0.062 (433 hom., cov: 31)
  • Exomes 𝑓: 0.071 (901 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• 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), G2P, ClinGen

DTNBP1-AS1 (HGNC:58090):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0875 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.512-12587G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.461-12587G>A		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.407-12587G>A		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.512-12587G>A		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.407-12587G>A		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.512-12587G>A		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9445 AN: 151752 Hom.: 432 Cov.: 31

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0570

GnomAD4 exome AF: 0.0712 AC: 20210 AN: 283708 Hom.: 901 AF XY: 0.0674 AC XY: 11023 AN XY: 163502

African (AFR) AF: 0.0110 AC: 74 AN: 6716

American (AMR) AF: 0.118 AC: 2533 AN: 21444

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 317 AN: 9686

East Asian (EAS) AF: 0.000658 AC: 6 AN: 9122

South Asian (SAS) AF: 0.0435 AC: 2493 AN: 57264

European-Finnish (FIN) AF: 0.138 AC: 1629 AN: 11818

Middle Eastern (MID) AF: 0.0211 AC: 55 AN: 2606

European-Non Finnish (NFE) AF: 0.0805 AC: 12235 AN: 152016

Other (OTH) AF: 0.0666 AC: 868 AN: 13036

GnomAD4 genome AF: 0.0622 AC: 9450 AN: 151852 Hom.: 433 Cov.: 31 AF XY: 0.0653 AC XY: 4845 AN XY: 74184

African (AFR) AF: 0.0148 AC: 613 AN: 41408

American (AMR) AF: 0.0914 AC: 1394 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.0391 AC: 188 AN: 4806

European-Finnish (FIN) AF: 0.145 AC: 1513 AN: 10456

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0803 AC: 5456 AN: 67986

Other (OTH) AF: 0.0564 AC: 119 AN: 2110

Alfa AF: 0.0731 Hom.: 813

Bravo AF: 0.0565

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.28
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: rs12527121; hg19: chr6-15546213;