10-93757865-G-C

Position:

• chr10-93757865-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000627420.2(LGI1):​c.-280G>C variant causes a 5 prime UTR, NMD transcript 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 5_prime_UTR, NMD_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.22

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1921 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGI1	ENST00000627420.2	c.-280G>C		5_prime_UTR_variant, NMD_transcript_variant	1/6	1
LGI1	ENST00000629035.2	c.-280G>C		5_prime_UTR_variant	1/7	5
LGI1	ENST00000478763.2			upstream_gene_variant		2
LGI1	ENST00000630487.2			upstream_gene_variant		3

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

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000335

Gnomad4 OTH exome AF: 0.00291

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

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00616

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.92

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: rs74150339; hg19: chr10-95517622;