rs2296434
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000195.5(HPS1):āc.1472C>Gā(p.Pro491Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,613,882 control chromosomes in the GnomAD database, including 7,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P491H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000195.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS1 | NM_000195.5 | c.1472C>G | p.Pro491Arg | missense_variant | 15/20 | ENST00000361490.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS1 | ENST00000361490.9 | c.1472C>G | p.Pro491Arg | missense_variant | 15/20 | 1 | NM_000195.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.101 AC: 15373AN: 152114Hom.: 827 Cov.: 32
GnomAD3 exomes AF: 0.107 AC: 26818AN: 251010Hom.: 1717 AF XY: 0.101 AC XY: 13658AN XY: 135740
GnomAD4 exome AF: 0.0903 AC: 132043AN: 1461650Hom.: 6496 Cov.: 34 AF XY: 0.0887 AC XY: 64518AN XY: 727128
GnomAD4 genome AF: 0.101 AC: 15395AN: 152232Hom.: 830 Cov.: 32 AF XY: 0.105 AC XY: 7811AN XY: 74408
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Pro491Arg in exon 15 of HPS1: This variant is not expected to have clinical sign ificance because it has been identified in 11.0% (484/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs2296434). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hermansky-Pudlak syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Hermansky-Pudlak syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at