10-98445350-G-T

Variant names:

Variant summary

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

The ENST00000467246.5(HPS1):n.-51C>A 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 0.285 in 152,854 control chromosomes in the GnomAD database, including 7,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7012 hom., cov: 32)

Exomes 𝑓: 0.32 ( 41 hom. )

Consequence

HPS1
ENST00000467246.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.83

Publications

9 publications found

Variant links:

Genes affected

HPS1 (HGNC:5163): (HPS1 biogenesis of lysosomal organelles complex 3 subunit 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is a component of three different protein complexes termed biogenesis of lysosome-related organelles complex (BLOC)-3, BLOC4, and BLOC5. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 1. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on chromosome 22. [provided by RefSeq, Aug 2015]

HPS1 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
Hermansky-Pudlak syndrome with pulmonary fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HPS1 links:

ENSG00000289758 (HGNC:):

ENSG00000289758 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=-0.62).

BP6

Variant 10-98445350-G-T is Benign according to our data. Variant chr10-98445350-G-T is described in ClinVar as Benign. ClinVar VariationId is 298358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS1	NM_000195.5 link	c.-51C>A		5_prime_UTR_variant	Exon 2 of 20	ENST00000361490.9	NP_000186.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000289758	ENST00000699159.1 link	n.-51C>A	non_coding_transcript_exon_variant	Exon 2 of 24			ENSP00000514167.1	A0A8V8TP71
HPS1	ENST00000361490.9 link	c.-51C>A	5_prime_UTR_variant	Exon 2 of 20	1	NM_000195.5	ENSP00000355310.4	Q92902-1
ENSG00000289758	ENST00000699159.1 link	n.-51C>A	5_prime_UTR_variant	Exon 2 of 24			ENSP00000514167.1	A0A8V8TP71

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43369

AN:

151972

Hom.:

7014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.325

AC:

248

AN:

764

Hom.:

Cov.:

AF XY:

0.344

AC XY:

152

AN XY:

442

show subpopulations

African (AFR)

AF:

0.111

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.391

AC:

AN:

156

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.306

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.315

AC:

140

AN:

444

Other (OTH)

AF:

0.278

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.285

AC:

43377

AN:

152090

Hom.:

7012

Cov.:

AF XY:

0.294

AC XY:

21857

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.145

AC:

6012

AN:

41506

American (AMR)

AF:

0.377

AC:

5766

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3470

East Asian (EAS)

AF:

0.427

AC:

2201

AN:

5150

South Asian (SAS)

AF:

0.421

AC:

2030

AN:

4820

European-Finnish (FIN)

AF:

0.407

AC:

4306

AN:

10578

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21094

AN:

67968

Other (OTH)

AF:

0.279

AC:

589

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1528

3056

4583

6111

7639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.285

Hom.:

2066

Bravo

AF:

0.274

Asia WGS

AF:

0.389

AC:

1352

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hermansky-Pudlak syndrome 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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