10-93758112-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005097.4(LGI1):​c.-33C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,587,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LGI1
NM_005097.4 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.95

Publications

0 publications found
Variant links:
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]
LGI1 Gene-Disease associations (from GenCC):
  • autosomal dominant epilepsy with auditory features
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • epilepsy, familial temporal lobe, 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 10-93758112-C-T is Benign according to our data. Variant chr10-93758112-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 506416.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGI1NM_005097.4 linkc.-33C>T 5_prime_UTR_variant Exon 1 of 8 ENST00000371418.9 NP_005088.1 O95970-1A0A0S2Z4S7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGI1ENST00000371418.9 linkc.-33C>T 5_prime_UTR_variant Exon 1 of 8 1 NM_005097.4 ENSP00000360472.4 O95970-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1435256
Hom.:
0
Cov.:
26
AF XY:
0.00000140
AC XY:
1
AN XY:
715714
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32978
American (AMR)
AF:
0.00
AC:
0
AN:
44586
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25956
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39536
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85618
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53342
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1088082
Other (OTH)
AF:
0.0000168
AC:
1
AN:
59456
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41402
American (AMR)
AF:
0.0000655
AC:
1
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10594
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 17, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Benign
0.91
PhyloP100
2.0
PromoterAI
-0.0080
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1444604152; hg19: chr10-95517869; API