rs9476887

Variant names:

• chr6-15662660-G-A
• rs9476887
• NM_032122.5:c.56+154C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-15662660-G-A
• chr6-15662660-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.56+154C>T		intron_variant	Intron 1 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.56+154C>T		intron_variant	Intron 1 of 9	1	NM_032122.5	ENSP00000341680.6

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

African (AFR) AF: 0.390 AC: 16140 AN: 41404

American (AMR) AF: 0.210 AC: 3204 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5160

South Asian (SAS) AF: 0.111 AC: 536 AN: 4820

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10598

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9248 AN: 67920

Other (OTH) AF: 0.186 AC: 394 AN: 2114

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

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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
PhyloP100		1.1
PromoterAI		0.46	Neutral
Mutation Taster		=98/2	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: rs9476887; hg19: chr6-15662891; COSMIC: COSV59044283;