rs11855874

Positions:

• chr15-77679568-A-G

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-98-2394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,242 control chromosomes in the GnomAD database, including 1,372 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 0.13 (1372 hom., cov: 32)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

Genes affected

LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_001301186.2	c.-98-2394T>C		intron_variant
LINGO1	NM_001301187.2	c.-98-2394T>C		intron_variant
LINGO1	NM_001301189.2	c.-98-2394T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000561030.5	c.-98-2394T>C		intron_variant		1		P4
LINGO1	ENST00000559893.5	c.-98-2394T>C		intron_variant		4
LINGO1	ENST00000561686.5	c.-13+11152T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19649 AN: 152124 Hom.: 1376 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19655 AN: 152242 Hom.: 1372 Cov.: 32 AF XY: 0.131 AC XY: 9727 AN XY: 74436

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.154

Alfa AF: 0.142 Hom.: 317

Bravo AF: 0.136

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11855874; hg19: chr15-77971910;