10-93757841-C-T

Variant names:

• chr10-93757841-C-T
• rs886047484
• ENST00000627420.2:n.-304C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BS1_Supporting BS2

The ENST00000627420.2(LGI1):​n.-304C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000111 in 386,264 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: LGI1 ENST00000627420.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25
• Publications: 0 publications found

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)

ENSG00000303320 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000202 (3/148376) while in subpopulation EAS AF = 0.000605 (3/4958). AF 95% confidence interval is 0.000164. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAdExome4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI1	NM_005097.4	c.-304C>T		upstream_gene_variant		ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.-304C>T		upstream_gene_variant		1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes AF: 0.0000202 AC: 3 AN: 148376 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000605

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: 0.000168 AC: 40 AN: 237888 Hom.: 0 Cov.: 0 AF XY: 0.000118 AC XY: 15 AN XY: 127332

African (AFR) AF: 0.00 AC: 0 AN: 7138

American (AMR) AF: 0.00 AC: 0 AN: 11298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6538

East Asian (EAS) AF: 0.00308 AC: 39 AN: 12668

South Asian (SAS) AF: 0.00 AC: 0 AN: 35636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 866

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 139528

Other (OTH) AF: 0.0000772 AC: 1 AN: 12956

GnomAD4 genome AF: 0.0000202 AC: 3 AN: 148376 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 71968

African (AFR) AF: 0.00 AC: 0 AN: 40134

American (AMR) AF: 0.00 AC: 0 AN: 14258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000605 AC: 3 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, familial temporal lobe, 1 Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		5.3
PromoterAI		-0.29	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

Other links and lift over

dbSNP: rs886047484; hg19: chr10-95517598;