ENST00000626307.1:n.757T>G

Variant names:

• chr10-93789081-T-G
• rs1538599
• ENST00000626307.1:n.757T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000626307.1(LGI1):​n.757T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,098 control chromosomes in the GnomAD database, including 54,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (54285 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: LGI1 ENST00000626307.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000626307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	NM_005097.4	MANE Select	c.432-1018T>G		intron	N/A	NP_005088.1
	LGI1	NM_001308276.2		c.288-1018T>G		intron	N/A	NP_001295205.1
	LGI1	NM_001308275.2		c.432-1018T>G		intron	N/A	NP_001295204.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	ENST00000626307.1	TSL:1	n.757T>G		non_coding_transcript_exon	Exon 1 of 3
	LGI1	ENST00000371418.9	TSL:1 MANE Select	c.432-1018T>G		intron	N/A	ENSP00000360472.4
	LGI1	ENST00000371413.4	TSL:1	c.432-1018T>G		intron	N/A	ENSP00000360467.3

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123325 AN: 151978 Hom.: 54276 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.838

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.811 AC: 123352 AN: 152096 Hom.: 54285 Cov.: 31 AF XY: 0.815 AC XY: 60616 AN XY: 74360

African (AFR) AF: 0.428 AC: 17712 AN: 41408

American (AMR) AF: 0.912 AC: 13950 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3311 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4996 AN: 5178

South Asian (SAS) AF: 0.932 AC: 4490 AN: 4816

European-Finnish (FIN) AF: 0.951 AC: 10069 AN: 10584

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 65958 AN: 68032

Other (OTH) AF: 0.838 AC: 1764 AN: 2104

Alfa AF: 0.860 Hom.: 7588

Bravo AF: 0.790

Asia WGS AF: 0.919 AC: 3198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.62
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1538599; hg19: chr10-95548838;