rs2743861

Variant names:

• chr6-15644815-A-C
• rs2743861
• NM_032122.5:c.161+6498T>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+6498T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,970 control chromosomes in the GnomAD database, including 1,601 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 0.13 (1601 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.161+6498T>G		intron_variant	Intron 3 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.161+6498T>G		intron_variant	Intron 3 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19590 AN: 151852 Hom.: 1604 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.129 AC: 19617 AN: 151970 Hom.: 1601 Cov.: 32 AF XY: 0.127 AC XY: 9427 AN XY: 74326

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.124

Alfa AF: 0.101 Hom.: 163

Bravo AF: 0.140

Asia WGS AF: 0.113 AC: 391 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.62

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: rs2743861; hg19: chr6-15645046; COSMIC: COSV59038534;