dbSNP rs11558324: DTNBP1:n.-18A>G (chr6-15662887-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000506844.1(DTNBP1):n.-18A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,603,324 control chromosomes in the GnomAD database, including 40,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3008 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37470 hom. )

Consequence

DTNBP1
ENST00000506844.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.80

Publications

7 publications found

Variant links:

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

DTNBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-15662887-T-C is Benign according to our data. Variant chr6-15662887-T-C is described in ClinVar as Benign. ClinVar VariationId is 262009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.-18A>G		5_prime_UTR_variant	Exon 1 of 10	ENST00000344537.10	NP_115498.2	Q96EV8-1A0A0S2Z5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 link	c.-18A>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28117

AN:

151922

Hom.:

3006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0845

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.174

AC:

41003

AN:

235784

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.000506

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.218

AC:

316792

AN:

1451288

Hom.:

37470

Cov.:

AF XY:

0.215

AC XY:

155493

AN XY:

722508

show subpopulations

African (AFR)

AF:

0.127

AC:

4260

AN:

33420

American (AMR)

AF:

0.132

AC:

5890

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

6860

AN:

26084

East Asian (EAS)

AF:

0.000605

AC:

AN:

39674

South Asian (SAS)

AF:

0.0904

AC:

7792

AN:

86232

European-Finnish (FIN)

AF:

0.157

AC:

6875

AN:

43810

Middle Eastern (MID)

AF:

0.177

AC:

1021

AN:

5756

European-Non Finnish (NFE)

AF:

0.245

AC:

271810

AN:

1111366

Other (OTH)

AF:

0.203

AC:

12260

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14669

29338

44006

58675

73344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8910

17820

26730

35640

44550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28127

AN:

152036

Hom.:

3008

Cov.:

AF XY:

0.177

AC XY:

13191

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.130

AC:

5405

AN:

41486

American (AMR)

AF:

0.165

AC:

2526

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

908

AN:

3470

East Asian (EAS)

AF:

0.00155

AC:

AN:

5168

South Asian (SAS)

AF:

0.0852

AC:

411

AN:

4824

European-Finnish (FIN)

AF:

0.149

AC:

1581

AN:

10580

Middle Eastern (MID)

AF:

0.209

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.244

AC:

16536

AN:

67904

Other (OTH)

AF:

0.192

AC:

405

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1184

2368

3552

4736

5920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

738

Bravo

AF:

0.186

Asia WGS

AF:

0.0510

AC:

178

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.1

(source)

DANN

Benign

0.85

PhyloP100

-1.8

PromoterAI

-0.074

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over