rs141197189
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000081.4(LYST):c.5923-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,561,406 control chromosomes in the GnomAD database, including 1,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.030 ( 99 hom., cov: 32)
Exomes 𝑓: 0.044 ( 1669 hom. )
Consequence
LYST
NM_000081.4 intron
NM_000081.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0930
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 1-235766296-C-A is Benign according to our data. Variant chr1-235766296-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 254930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.5923-19G>T | intron_variant | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.5923-19G>T | intron_variant | 5 | NM_000081.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0305 AC: 4639AN: 152024Hom.: 99 Cov.: 32
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GnomAD3 exomes AF: 0.0306 AC: 6986AN: 228040Hom.: 136 AF XY: 0.0313 AC XY: 3890AN XY: 124422
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GnomAD4 exome AF: 0.0442 AC: 62349AN: 1409264Hom.: 1669 Cov.: 26 AF XY: 0.0434 AC XY: 30477AN XY: 702872
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GnomAD4 genome ? AF: 0.0305 AC: 4640AN: 152142Hom.: 99 Cov.: 32 AF XY: 0.0290 AC XY: 2156AN XY: 74378
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Chédiak-Higashi syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at