rs143132529
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_005097.4(LGI1):c.216-55T>C variant causes a intron change. The variant allele was found at a frequency of 0.00819 in 1,210,304 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0066 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0084 ( 45 hom. )
Consequence
LGI1
NM_005097.4 intron
NM_005097.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
LGI1 (HGNC:6572): (leucine rich glioma inactivated 1) This gene encodes a member of the secreted leucine-rich repeat (LRR) superfamily and shares homology with members of the SLIT protein family. The encoded protein may regulate the activity of voltage-gated potassium channels and may be involved in neuronal growth regulation and cell survival. This gene is rearranged as a result of translocations in glioblastoma cell lines, and it is frequently down-regulated or rearranged in malignant gliomas. Mutations in this gene result in autosomal dominant lateral temporal epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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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=-0.44).
BP6
?
Variant 10-93758705-T-C is Benign according to our data. Variant chr10-93758705-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93758705-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0066 (1005/152344) while in subpopulation NFE AF= 0.00963 (655/68018). AF 95% confidence interval is 0.00902. There are 5 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1005 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LGI1 | NM_005097.4 | c.216-55T>C | intron_variant | ENST00000371418.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LGI1 | ENST00000371418.9 | c.216-55T>C | intron_variant | 1 | NM_005097.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00660 AC: 1005AN: 152226Hom.: 5 Cov.: 32
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GnomAD4 exome AF: 0.00842 AC: 8905AN: 1057960Hom.: 45 Cov.: 14 AF XY: 0.00827 AC XY: 4506AN XY: 544822
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GnomAD4 genome ? AF: 0.00660 AC: 1005AN: 152344Hom.: 5 Cov.: 32 AF XY: 0.00652 AC XY: 486AN XY: 74512
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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
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 13, 2017 | - - |
Autosomal dominant epilepsy with auditory features Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | LGI1: BS1, BS2 - |
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