rs143132529
Positions:
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]
Genome browser will be placed here
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. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1005 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LGI1 | NM_005097.4 | c.216-55T>C | intron_variant | ENST00000371418.9 | NP_005088.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00660 AC: 1005AN: 152226Hom.: 5 Cov.: 32
GnomAD3 genomes
AF:
AC:
1005
AN:
152226
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00842 AC: 8905AN: 1057960Hom.: 45 Cov.: 14 AF XY: 0.00827 AC XY: 4506AN XY: 544822
GnomAD4 exome
AF:
AC:
8905
AN:
1057960
Hom.:
Cov.:
14
AF XY:
AC XY:
4506
AN XY:
544822
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00660 AC: 1005AN: 152344Hom.: 5 Cov.: 32 AF XY: 0.00652 AC XY: 486AN XY: 74512
GnomAD4 genome
AF:
AC:
1005
AN:
152344
Hom.:
Cov.:
32
AF XY:
AC XY:
486
AN XY:
74512
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | LGI1: BS1, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at