rs11591594

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000195.5(HPS1):c.399-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,538,246 control chromosomes in the GnomAD database, including 20,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.13 ( 1516 hom., cov: 31)

Exomes 𝑓: 0.16 ( 19273 hom. )

Consequence

HPS1
NM_000195.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.39

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 links:

ENSG00000289758 (HGNC:):

ENSG00000289758 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-98434126-C-T is Benign according to our data. Variant chr10-98434126-C-T is described in ClinVar as [Benign]. Clinvar id is 255503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS1	NM_000195.5 link	c.399-35G>A		intron_variant	Intron 5 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.399-35G>A		intron_variant	Intron 5 of 19	1	NM_000195.5	ENSP00000355310.4		Q92902-1
ENSG00000289758	ENST00000699159.1 link	n.399-35G>A		intron_variant	Intron 5 of 23			ENSP00000514167.1		A0A8V8TP71

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19501

AN:

152004

Hom.:

1518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0925

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.143

AC:

20465

AN:

142816

Hom.:

1709

AF XY:

0.151

AC XY:

11616

AN XY:

76858

show subpopulations

Gnomad AFR exome

AF:

0.0537

Gnomad AMR exome

AF:

0.0702

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.163

AC:

226344

AN:

1386124

Hom.:

19273

Cov.:

AF XY:

0.165

AC XY:

112852

AN XY:

683668

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

Gnomad4 AMR exome

AF:

0.0717

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.0879

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.128

AC:

19504

AN:

152122

Hom.:

1516

Cov.:

AF XY:

0.129

AC XY:

9562

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0609

Gnomad4 AMR

AF:

0.0924

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.143

Hom.:

387

Bravo

AF:

0.117

Asia WGS

AF:

0.140

AC:

484

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 27, 2018

GeneDx

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:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome 1

Benign:1

Jul 10, 2021

Genome-Nilou Lab

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

-0.88

CADD

Benign

1.2

DANN

Benign

0.44

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over