6-15569775-G-A

Position:

• chr6-15569775-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032122.5(DTNBP1):​c.511+23284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,064 control chromosomes in the GnomAD database, including 81 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 0.031 (81 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282

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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0305 (4639/152064) while in subpopulation NFE AF= 0.0482 (3275/68000). AF 95% confidence interval is 0.0468. There are 81 homozygotes in gnomad4. There are 2205 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 81 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.511+23284C>T		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+23284C>T		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4640 AN: 151946 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00742

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0305 AC: 4639 AN: 152064 Hom.: 81 Cov.: 32 AF XY: 0.0297 AC XY: 2205 AN XY: 74330

Gnomad4 AFR AF: 0.00740

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0210 Hom.: 7

Bravo AF: 0.0263

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.61

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: rs7771339; hg19: chr6-15570006;