rs41308172
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_000081.4(LYST):​c.10800+4G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,612,438 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: đť‘“ 0.0045 ( 6 hom., cov: 32)
Exomes đť‘“: 0.0067 ( 44 hom. )
Consequence
LYST
NM_000081.4 splice_donor_region, intron
NM_000081.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.009497
2
Clinical Significance
Conservation
PhyloP100: 0.384
Genes affected
LYST (HGNC:1968): (lysosomal trafficking regulator) This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.2).
BP6
Variant 1-235686945-C-A is Benign according to our data. Variant chr1-235686945-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 296350.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Benign=2, Uncertain_significance=1}. Variant chr1-235686945-C-A is described in Lovd as [Benign]. Variant chr1-235686945-C-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00449 (684/152328) while in subpopulation NFE AF= 0.00681 (463/68026). AF 95% confidence interval is 0.00629. There are 6 homozygotes in gnomad4. There are 307 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.10800+4G>T | splice_donor_region_variant, intron_variant | ENST00000389793.7 | NP_000072.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.10800+4G>T | splice_donor_region_variant, intron_variant | 5 | NM_000081.4 | ENSP00000374443 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00451 AC: 686AN: 152210Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00643 AC: 1618AN: 251454Hom.: 11 AF XY: 0.00617 AC XY: 838AN XY: 135902
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GnomAD4 exome AF: 0.00669 AC: 9763AN: 1460110Hom.: 44 Cov.: 30 AF XY: 0.00665 AC XY: 4829AN XY: 726498
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GnomAD4 genome AF: 0.00449 AC: 684AN: 152328Hom.: 6 Cov.: 32 AF XY: 0.00412 AC XY: 307AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 09, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | LYST: BP4, BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2021 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 03, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 28, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at