rs1801287

Variant names:

• chr10-98431163-G-A
• rs1801287
• NM_000195.5:c.636C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-98431163-G-A
• chr10-98431163-G-C
• chr10-98431163-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000195.5(HPS1):​c.636C>T​(p.Leu212Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,542 control chromosomes in the GnomAD database, including 75,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L212L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (6026 hom., cov: 33)
  • Exomes 𝑓: 0.30 (69024 hom.)
• Consequence: HPS1 NM_000195.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.69
• Publications: 15 publications found

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]

ENSG00000289758 (HGNC:):

MIR4685 (HGNC:41802): (microRNA 4685) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.086).
• BP6: Variant 10-98431163-G-A is Benign according to our data. Variant chr10-98431163-G-A is described in ClinVar as Benign. ClinVar VariationId is 167185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS1	NM_000195.5	c.636C>T	p.Leu212Leu	synonymous_variant	Exon 7 of 20	ENST00000361490.9	NP_000186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS1	ENST00000361490.9	c.636C>T	p.Leu212Leu	synonymous_variant	Exon 7 of 20	1	NM_000195.5	ENSP00000355310.4
ENSG00000289758	ENST00000699159.1	n.*94C>T		non_coding_transcript_exon_variant	Exon 7 of 24			ENSP00000514167.1
ENSG00000289758	ENST00000699159.1	n.*94C>T		3_prime_UTR_variant	Exon 7 of 24			ENSP00000514167.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40425 AN: 152020 Hom.: 6028 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.316 AC: 78552 AN: 248344 AF XY: 0.325

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.303 AC: 442519 AN: 1461404 Hom.: 69024 Cov.: 38 AF XY: 0.308 AC XY: 223610 AN XY: 727002

African (AFR) AF: 0.136 AC: 4546 AN: 33478

American (AMR) AF: 0.334 AC: 14896 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7491 AN: 26132

East Asian (EAS) AF: 0.340 AC: 13498 AN: 39662

South Asian (SAS) AF: 0.427 AC: 36785 AN: 86224

European-Finnish (FIN) AF: 0.347 AC: 18529 AN: 53356

Middle Eastern (MID) AF: 0.328 AC: 1890 AN: 5768

European-Non Finnish (NFE) AF: 0.294 AC: 326897 AN: 1111736

Other (OTH) AF: 0.298 AC: 17987 AN: 60384

GnomAD4 genome AF: 0.266 AC: 40434 AN: 152138 Hom.: 6026 Cov.: 33 AF XY: 0.273 AC XY: 20272 AN XY: 74362

African (AFR) AF: 0.141 AC: 5859 AN: 41536

American (AMR) AF: 0.320 AC: 4888 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1778 AN: 5156

South Asian (SAS) AF: 0.403 AC: 1941 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3863 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20231 AN: 67988

Other (OTH) AF: 0.263 AC: 555 AN: 2114

Alfa AF: 0.282 Hom.: 19190

Bravo AF: 0.253

Asia WGS AF: 0.340 AC: 1180 AN: 3478

EpiCase AF: 0.297

EpiControl AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu212Leu in exon 7 of HPS1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 29.2% (2515/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1801287). -

Feb 26, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome 1 Benign:2

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.25
DANN	Benign	0.87
PhyloP100		-1.7
PromoterAI		0.033	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1801287; hg19: chr10-100190920; COSMIC: COSV57266367; COSMIC: COSV57266367;