Variant 10-93792896-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005097.4(LGI1):c.657T>C(p.Phe219=) 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:2

Conservation

PhyloP100: 2.31

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1164242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93792896-T-C is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGI1	NM_005097.4 linkuse as main transcript	c.657T>C	p.Phe219=	synonymous_variant	6/8	ENST00000371418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGI1	ENST00000371418.9 linkuse as main transcript	c.657T>C	p.Phe219=	synonymous_variant	6/8	1	NM_005097.4	P1	O95970-1

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

GnomAD3 exomes

AF:

0.994

AC:

249854

AN:

251436

Hom.:

124178

AF XY:

0.995

AC XY:

135197

AN XY:

135888

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 SAS 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

Gnomad4 AFR exome

AF:

0.925

Gnomad4 AMR exome

AF:

0.993

Gnomad4 ASJ exome

AF:

0.990

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.978

AC:

148923

AN:

152222

Hom.:

72926

Cov.:

AF XY:

0.979

AC XY:

72887

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.987

Gnomad4 ASJ

AF:

0.990

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.982

Alfa

AF:

0.993

Hom.:

93918

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant epilepsy with auditory features

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Epilepsy, familial temporal lobe, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.2

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over