Variant 10-98416397-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000195.5(HPS1):c.*1167G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,186 control chromosomes in the GnomAD database, including 10,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10582 hom., cov: 33)

Exomes 𝑓: 0.32 ( 10 hom. )

Consequence

HPS1
NM_000195.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-98416397-C-T is Benign according to our data. Variant chr10-98416397-C-T is described in ClinVar as [Benign]. Clinvar id is 298311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS1	NM_000195.5 linkuse as main transcript	c.*1167G>A		3_prime_UTR_variant	20/20	ENST00000361490.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS1	ENST00000361490.9 linkuse as main transcript	c.*1167G>A		3_prime_UTR_variant	20/20	1	NM_000195.5	P1	Q92902-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53849

AN:

151890

Hom.:

10566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.330

GnomAD4 exome

AF:

0.320

AC:

AN:

178

Hom.:

Cov.:

AF XY:

0.357

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.355

AC:

53914

AN:

152008

Hom.:

10582

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.285

Hom.:

6624

Bravo

AF:

0.368

Asia WGS

AF:

0.451

AC:

1565

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hermansky-Pudlak syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.94

CADD

Benign

0.11

DANN

Benign

0.36

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