Variant rs2296430 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.118-54A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,610,376 control chromosomes in the GnomAD database, including 75,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9089 hom., cov: 31)

Exomes 𝑓: 0.30 ( 66518 hom. )

Consequence

HPS1
NM_000195.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.210

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 10-98435826-T-A is Benign according to our data. Variant chr10-98435826-T-A is described in ClinVar as [Benign]. Clinvar id is 1180583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS1	NM_000195.5 linkuse as main transcript	c.118-54A>T		intron_variant		ENST00000361490.9	NP_000186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS1	ENST00000361490.9 linkuse as main transcript	c.118-54A>T		intron_variant		1	NM_000195.5	ENSP00000355310	P1	Q92902-1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50500

AN:

151618

Hom.:

9078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.298

AC:

434081

AN:

1458642

Hom.:

66518

AF XY:

0.299

AC XY:

217336

AN XY:

725788

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.345

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.333

AC:

50546

AN:

151734

Hom.:

9089

Cov.:

AF XY:

0.329

AC XY:

24385

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.465

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.308

Hom.:

966

Bravo

AF:

0.333

Asia WGS

AF:

0.334

AC:

1159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Hermansky-Pudlak syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.5

DANN

Benign

0.49

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