rs12571249

Variant names:

Variant summary

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

The NM_000195.5(HPS1):c.987+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,550,062 control chromosomes in the GnomAD database, including 1,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 363 hom., cov: 33)

Exomes 𝑓: 0.015 ( 680 hom. )

Consequence

HPS1
NM_000195.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.962

Publications

4 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=-0.92).

BP6

Variant 10-98427202-A-G is Benign according to our data. Variant chr10-98427202-A-G is described in ClinVar as Benign. ClinVar VariationId is 255506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS1	NM_000195.5 link	c.987+13T>C		intron_variant	Intron 11 of 19	ENST00000361490.9	NP_000186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS1	ENST00000361490.9 link	c.987+13T>C		intron_variant	Intron 11 of 19	1	NM_000195.5	ENSP00000355310.4		Q92902-1
ENSG00000289758	ENST00000699159.1 link	n.*346+13T>C		intron_variant	Intron 10 of 23			ENSP00000514167.1		A0A8V8TP71

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6801

AN:

152218

Hom.:

362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.0856

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00708

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0283

AC:

4416

AN:

156290

AF XY:

0.0296

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.00987

Gnomad ASJ exome

AF:

0.00720

Gnomad EAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00659

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0150

AC:

20999

AN:

1397726

Hom.:

680

Cov.:

AF XY:

0.0162

AC XY:

11188

AN XY:

689522

show subpopulations

African (AFR)

AF:

0.128

AC:

4054

AN:

31550

American (AMR)

AF:

0.0124

AC:

441

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.00708

AC:

178

AN:

25152

East Asian (EAS)

AF:

0.0562

AC:

2016

AN:

35842

South Asian (SAS)

AF:

0.0680

AC:

5382

AN:

79162

European-Finnish (FIN)

AF:

0.000937

AC:

AN:

49084

Middle Eastern (MID)

AF:

0.0162

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00677

AC:

7299

AN:

1077592

Other (OTH)

AF:

0.0257

AC:

1491

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

890

1780

2670

3560

4450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.0448

AC:

6822

AN:

152336

Hom.:

363

Cov.:

AF XY:

0.0443

AC XY:

3300

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.122

AC:

5079

AN:

41570

American (AMR)

AF:

0.0225

AC:

345

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.0745

AC:

386

AN:

5178

South Asian (SAS)

AF:

0.0854

AC:

413

AN:

4834

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00709

AC:

482

AN:

68028

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

327

654

981

1308

1635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0214

Hom.:

Bravo

AF:

0.0487

Asia WGS

AF:

0.0930

AC:

322

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

987+13T>C in intron 11 of HPS1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 10.8% (448/4134) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs12571249). -

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

-0.92

CADD

Benign

0.015

(source)

DANN

Benign

0.22

PhyloP100

-0.96

Mutation Taster

=100/0

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