10-93757865-G-C

Variant names:

• chr10-93757865-G-C
• rs74150339
• ENST00000627420.2:n.-280G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000627420.2(LGI1):​n.-280G>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00496 in 502,076 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (9 hom.)
• Consequence: LGI1 ENST00000627420.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.22
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 10-93757865-G-C is Benign according to our data. Variant chr10-93757865-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 301651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1921/152214) while in subpopulation AFR AF = 0.0448 (1860/41514). AF 95% confidence interval is 0.0431. There are 43 homozygotes in GnomAd4. There are 913 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1921 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI1	NM_005097.4	c.-280G>C		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.-280G>C		upstream_gene_variant		1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1920 AN: 152096 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

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: 0.0000588

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.00163 AC: 570 AN: 349862 Hom.: 9 Cov.: 0 AF XY: 0.00130 AC XY: 242 AN XY: 185594

African (AFR) AF: 0.0458 AC: 469 AN: 10242

American (AMR) AF: 0.00218 AC: 34 AN: 15562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10490

East Asian (EAS) AF: 0.00 AC: 0 AN: 22104

South Asian (SAS) AF: 0.0000236 AC: 1 AN: 42332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19050

Middle Eastern (MID) AF: 0.000665 AC: 1 AN: 1504

European-Non Finnish (NFE) AF: 0.0000335 AC: 7 AN: 208656

Other (OTH) AF: 0.00291 AC: 58 AN: 19922

GnomAD4 genome AF: 0.0126 AC: 1921 AN: 152214 Hom.: 43 Cov.: 32 AF XY: 0.0123 AC XY: 913 AN XY: 74428

African (AFR) AF: 0.0448 AC: 1860 AN: 41514

American (AMR) AF: 0.00288 AC: 44 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.000283 Hom.: 0

Bravo AF: 0.0145

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, familial temporal lobe, 1 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

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	-0.29
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		6.2
PromoterAI		-0.077	Neutral
Mutation Taster		=285/15	polymorphism

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: rs74150339; hg19: chr10-95517622;