chr22-50080294-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015166.4(MLC1):c.321+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,562,152 control chromosomes in the GnomAD database, including 680,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.95 ( 68863 hom., cov: 33)
Exomes 𝑓: 0.93 ( 611747 hom. )
Consequence
MLC1
NM_015166.4 intron
NM_015166.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
Genes affected
MLC1 (HGNC:17082): (modulator of VRAC current 1) The function of this gene product is unknown; however, homology to other proteins suggests that it may be an integral membrane transporter. Mutations in this gene have been associated with megalencephalic leukoencephalopathy with subcortical cysts, an autosomal recessive neurological disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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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=-0.94).
BP6
?
Variant 22-50080294-A-G is Benign according to our data. Variant chr22-50080294-A-G is described in ClinVar as [Benign]. Clinvar id is 260573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLC1 | NM_015166.4 | c.321+50T>C | intron_variant | ENST00000311597.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLC1 | ENST00000311597.10 | c.321+50T>C | intron_variant | 1 | NM_015166.4 | P1 | |||
MLC1 | ENST00000395876.6 | c.321+50T>C | intron_variant | 1 | P1 | ||||
MLC1 | ENST00000442311.1 | c.231+50T>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.950 AC: 144630AN: 152220Hom.: 68798 Cov.: 33
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GnomAD3 exomes AF: 0.949 AC: 192215AN: 202522Hom.: 91330 AF XY: 0.949 AC XY: 103036AN XY: 108614
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GnomAD4 exome AF: 0.931 AC: 1312951AN: 1409814Hom.: 611747 Cov.: 29 AF XY: 0.932 AC XY: 652305AN XY: 699760
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GnomAD4 genome ? AF: 0.950 AC: 144754AN: 152338Hom.: 68863 Cov.: 33 AF XY: 0.953 AC XY: 71021AN XY: 74496
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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:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Megalencephalic leukoencephalopathy with subcortical cysts 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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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