10-93789081-T-G

Position:

• chr10-93789081-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371418.9(LGI1):​c.432-1018T>G variant causes a intron 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 ENST00000371418.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI1	NM_005097.4	c.432-1018T>G		intron_variant		ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.432-1018T>G		intron_variant		1	NM_005097.4	ENSP00000360472.4

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

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.838

Alfa AF: 0.879 Hom.: 7518

Bravo AF: 0.790

Asia WGS AF: 0.919 AC: 3198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs1538599; hg19: chr10-95548838;