rs7768128

chr6-15648469-A-G

Variant summary

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

The NM_032122.5(DTNBP1):c.161+2844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,940 control chromosomes in the GnomAD database, including 3,254 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 0.19 (3254 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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 (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.161+2844T>C		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.161+2844T>C		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29584 AN: 151822 Hom.: 3251 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.195 AC: 29596 AN: 151940 Hom.: 3254 Cov.: 32 AF XY: 0.187 AC XY: 13916 AN XY: 74274

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.193

Alfa AF: 0.221 Hom.: 495

Bravo AF: 0.194

Asia WGS AF: 0.0510 AC: 176 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	4.2
Dann	Benign	0.77

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: rs7768128; hg19: chr6-15648700;