rs143132529

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.68

Publications

1 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)

LGI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1005 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI1	NM_005097.4 link	c.216-55T>C		intron_variant	Intron 1 of 7	ENST00000371418.9	NP_005088.1	O95970-1A0A0S2Z4S7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9 link	c.216-55T>C		intron_variant	Intron 1 of 7	1	NM_005097.4	ENSP00000360472.4		O95970-1

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1005

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00790

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00963

Gnomad OTH

AF:

0.00860

GnomAD4 exome

AF:

0.00842

AC:

8905

AN:

1057960

Hom.:

Cov.:

AF XY:

0.00827

AC XY:

4506

AN XY:

544822

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

25944

American (AMR)

AF:

0.00621

AC:

270

AN:

43510

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

347

AN:

23606

East Asian (EAS)

AF:

0.00

AC:

AN:

37822

South Asian (SAS)

AF:

0.00115

AC:

AN:

77536

European-Finnish (FIN)

AF:

0.00897

AC:

434

AN:

48364

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.00964

AC:

7229

AN:

749712

Other (OTH)

AF:

0.00900

AC:

423

AN:

46994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

481

962

1443

1924

2405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00660

AC:

1005

AN:

152344

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

486

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41580

American (AMR)

AF:

0.00719

AC:

110

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00790

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00963

AC:

655

AN:

68018

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00907

Hom.:

Bravo

AF:

0.00629

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LGI1: BS2 -

not specified

Benign:1

Jan 13, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant epilepsy with auditory features

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epilepsy, familial temporal lobe, 1

Benign:1

Nov 07, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

3.7

Mutation Taster

=100/0

polymorphism

(source)

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

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rs143132529

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over