chr1-235661109-T-G
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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.*1831A>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00323 in 152,216 control chromosomes in the GnomAD database, including 3 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‘“ 0.0032 ( 3 hom., cov: 32)
Exomes đť‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LYST
NM_000081.4 3_prime_UTR
NM_000081.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.69
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=-0.26).
BP6
Variant 1-235661109-T-G is Benign according to our data. Variant chr1-235661109-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 296319.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00323 (492/152216) while in subpopulation AFR AF= 0.01 (417/41544). AF 95% confidence interval is 0.00924. There are 3 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.*1831A>C | 3_prime_UTR_variant | 53/53 | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.*1831A>C | 3_prime_UTR_variant | 53/53 | 5 | NM_000081.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00323 AC: 492AN: 152098Hom.: 3 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 432Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 260
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GnomAD4 genome AF: 0.00323 AC: 492AN: 152216Hom.: 3 Cov.: 32 AF XY: 0.00310 AC XY: 231AN XY: 74402
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | LYST: BS1, BS2 - |
Computational scores
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Name
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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