rs143132529

Positions:

• chr10-93758705-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005097.4(LGI1):​c.216-55T>C variant causes a intron change. The variant allele was found at a frequency of 0.00819 in 1,210,304 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (45 hom.)
• Consequence: LGI1 NM_005097.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.68

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-93758705-T-C is Benign according to our data. Variant chr10-93758705-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93758705-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0066 (1005/152344) while in subpopulation NFE AF= 0.00963 (655/68018). AF 95% confidence interval is 0.00902. There are 5 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1005 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI1	NM_005097.4	c.216-55T>C		intron_variant		ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.216-55T>C		intron_variant		1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes AF: 0.00660 AC: 1005 AN: 152226 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00790

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00842 AC: 8905 AN: 1057960 Hom.: 45 Cov.: 14 AF XY: 0.00827 AC XY: 4506 AN XY: 544822

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00621

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00897

Gnomad4 NFE exome AF: 0.00964

Gnomad4 OTH exome AF: 0.00900

GnomAD4 genome AF: 0.00660 AC: 1005 AN: 152344 Hom.: 5 Cov.: 32 AF XY: 0.00652 AC XY: 486 AN XY: 74512

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00790

Gnomad4 NFE AF: 0.00963

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00907 Hom.: 0

Bravo AF: 0.00629

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	LGI1: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 13, 2017

- -

Autosomal dominant epilepsy with auditory features Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.85

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: rs143132529; hg19: chr10-95518462;