rs9476887

chr6-15662660-G-Achr6-15662660-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032122.5(DTNBP1):c.56+154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,970 control chromosomes in the GnomAD database, including 4,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (4280 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 6-15662660-G-A is Benign according to our data. Variant chr6-15662660-G-A is described in ClinVar as [Benign]. Clinvar id is 1225118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.56+154C>T		intron_variant		ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.56+154C>T		intron_variant		1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30841 AN: 151852 Hom.: 4284 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.203 AC: 30855 AN: 151970 Hom.: 4280 Cov.: 32 AF XY: 0.198 AC XY: 14683 AN XY: 74298

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.186

Alfa AF: 0.0637 Hom.: 91

Bravo AF: 0.222

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
Dann	Benign	0.96

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: rs9476887; hg19: chr6-15662891; COSMIC: COSV59044283;