rs143132529

Variant names:

• chr10-93758705-T-C
• rs143132529
• NM_005097.4:c.216-55T>C

Variant summary

Our verdict is Benign. The variant received -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:5
• Conservation: PhyloP100: 3.68
• 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)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 464748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1005 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005097.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	NM_005097.4	MANE Select	c.216-55T>C		intron	N/A	NP_005088.1	O95970-1
	LGI1	NM_001308276.2		c.216-55T>C		intron	N/A	NP_001295205.1	O95970-3
	LGI1	NM_001308275.2		c.216-55T>C		intron	N/A	NP_001295204.1	O95970-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	ENST00000371418.9	TSL:1 MANE Select	c.216-55T>C		intron	N/A	ENSP00000360472.4	O95970-1
	LGI1	ENST00000371413.4	TSL:1	c.216-55T>C		intron	N/A	ENSP00000360467.3	O95970-2
	LGI1	ENST00000627420.2	TSL:1	n.*6-55T>C		intron	N/A	ENSP00000487116.1	A0A0D9SFS5

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

African (AFR) AF: 0.00143 AC: 37 AN: 25944

American (AMR) AF: 0.00621 AC: 270 AN: 43510

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 347 AN: 23606

East Asian (EAS) AF: 0.00 AC: 0 AN: 37822

South Asian (SAS) AF: 0.00115 AC: 89 AN: 77536

European-Finnish (FIN) AF: 0.00897 AC: 434 AN: 48364

Middle Eastern (MID) AF: 0.0170 AC: 76 AN: 4472

European-Non Finnish (NFE) AF: 0.00964 AC: 7229 AN: 749712

Other (OTH) AF: 0.00900 AC: 423 AN: 46994

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

African (AFR) AF: 0.00125 AC: 52 AN: 41580

American (AMR) AF: 0.00719 AC: 110 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00790 AC: 84 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00963 AC: 655 AN: 68018

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00907 Hom.: 0

Bravo AF: 0.00629

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant epilepsy with auditory features (1)
-	-	1	Epilepsy, familial temporal lobe, 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		3.7
Mutation Taster		=100/0	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: rs143132529; hg19: chr10-95518462;