rs7541057
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000081.4(LYST):c.10564+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,571,076 control chromosomes in the GnomAD database, including 195,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.53 ( 23488 hom., cov: 32)
Exomes 𝑓: 0.48 ( 172068 hom. )
Consequence
LYST
NM_000081.4 intron
NM_000081.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.88
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 1-235697040-C-T is Benign according to our data. Variant chr1-235697040-C-T is described in ClinVar as [Benign]. Clinvar id is 254908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.10564+43G>A | intron_variant | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.10564+43G>A | intron_variant | 5 | NM_000081.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.532 AC: 80881AN: 152004Hom.: 23439 Cov.: 32
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GnomAD3 exomes AF: 0.420 AC: 103367AN: 245900Hom.: 25505 AF XY: 0.412 AC XY: 54796AN XY: 132914
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GnomAD4 exome AF: 0.477 AC: 676800AN: 1418954Hom.: 172068 Cov.: 23 AF XY: 0.468 AC XY: 331761AN XY: 708282
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GnomAD4 genome ? AF: 0.532 AC: 80978AN: 152122Hom.: 23488 Cov.: 32 AF XY: 0.519 AC XY: 38594AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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