Genetic Variant LGI1:p.Phe219Phe (chr10-93792896-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005097.4(LGI1):c.657T>C(p.Phe219Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,614,040 control chromosomes in the GnomAD database, including 799,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72926 hom., cov: 30)

Exomes 𝑓: 1.0 ( 726800 hom. )

Consequence

LGI1
NM_005097.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.31

Publications

20 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-93792896-T-C is Benign according to our data. Variant chr10-93792896-T-C is described in ClinVar as Benign. ClinVar VariationId is 1164242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005097.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LGI1	NM_005097.4	MANE Select	c.657T>C	p.Phe219Phe	synonymous	Exon 6 of 8	NP_005088.1
LGI1	NM_001308276.2		c.513T>C	p.Phe171Phe	synonymous	Exon 4 of 6	NP_001295205.1
LGI1	NM_001308275.2		c.657T>C	p.Phe219Phe	synonymous	Exon 6 of 8	NP_001295204.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LGI1	ENST00000371418.9	TSL:1 MANE Select	c.657T>C	p.Phe219Phe	synonymous	Exon 6 of 8	ENSP00000360472.4
LGI1	ENST00000371413.4	TSL:1	c.657T>C	p.Phe219Phe	synonymous	Exon 6 of 8	ENSP00000360467.3
LGI1	ENST00000626307.1	TSL:1	n.4572T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

148821

AN:

152104

Hom.:

72880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.990

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.982

GnomAD2 exomes

AF:

0.994

AC:

249854

AN:

251436

AF XY:

0.995

show subpopulations

Gnomad AFR exome

AF:

0.930

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.997

AC:

1457602

AN:

1461818

Hom.:

726800

Cov.:

AF XY:

0.997

AC XY:

725364

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.925

AC:

30972

AN:

33472

American (AMR)

AF:

0.993

AC:

44420

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.990

AC:

25870

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39696

AN:

39698

South Asian (SAS)

AF:

1.00

AC:

86239

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

53418

AN:

53420

Middle Eastern (MID)

AF:

0.994

AC:

5734

AN:

5768

European-Non Finnish (NFE)

AF:

0.999

AC:

1111234

AN:

1111952

Other (OTH)

AF:

0.994

AC:

60019

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21668

43336

65004

86672

108340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.978

AC:

148923

AN:

152222

Hom.:

72926

Cov.:

AF XY:

0.979

AC XY:

72887

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.928

AC:

38524

AN:

41492

American (AMR)

AF:

0.987

AC:

15098

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.990

AC:

3437

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5162

AN:

5162

South Asian (SAS)

AF:

1.00

AC:

4822

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10614

AN:

10614

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67984

AN:

68038

Other (OTH)

AF:

0.982

AC:

2077

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

149

298

447

596

745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.989

Hom.:

139843

Bravo

AF:

0.975

Asia WGS

AF:

0.995

AC:

3459

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant epilepsy with auditory features

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Epilepsy, familial temporal lobe, 1

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.2

(source)

DANN

Benign

0.57

PhyloP100

2.3

Mutation Taster

=93/7

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over