rs2296435
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000195.5(HPS1):c.1599-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,612,042 control chromosomes in the GnomAD database, including 52,105 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
Consequence
NM_000195.5 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS1 | NM_000195.5 | c.1599-15A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000361490.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS1 | ENST00000361490.9 | c.1599-15A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000195.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.224 AC: 33978AN: 152018Hom.: 4242 Cov.: 33
GnomAD3 exomes AF: 0.271 AC: 67930AN: 250900Hom.: 9965 AF XY: 0.277 AC XY: 37602AN XY: 135766
GnomAD4 exome AF: 0.249 AC: 363790AN: 1459906Hom.: 47860 Cov.: 36 AF XY: 0.254 AC XY: 184776AN XY: 726354
GnomAD4 genome ? AF: 0.223 AC: 33993AN: 152136Hom.: 4245 Cov.: 33 AF XY: 0.228 AC XY: 16935AN XY: 74370
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 26, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 1599-15A>G in intron 16 of HPS1: This variant is not expected to have clinical s ignificance because it has been identified in 24.0% (2061/8600) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs2296435). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hermansky-Pudlak syndrome 1 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at