rs11856876

Positions:

• chr15-77680670-A-C
• chr15-77680670-A-T

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-98-3496T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,754 control chromosomes in the GnomAD database, including 13,143 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 0.40 (13143 hom., cov: 31)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-98-3496T>G		intron_variant			NP_001288115.1
LINGO1	NM_001301187.2	c.-98-3496T>G		intron_variant			NP_001288116.1
LINGO1	NM_001301189.2	c.-98-3496T>G		intron_variant			NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-98-3496T>G		intron_variant		1		ENSP00000453853	P4
LINGO1	ENST00000559893.5	c.-98-3496T>G		intron_variant		4		ENSP00000454051
LINGO1	ENST00000561686.5	c.-13+10050T>G		intron_variant		3		ENSP00000455605

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61282 AN: 151636 Hom.: 13132 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.404 AC: 61337 AN: 151754 Hom.: 13143 Cov.: 31 AF XY: 0.406 AC XY: 30111 AN XY: 74164

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.405

Alfa AF: 0.310 Hom.: 1803

Bravo AF: 0.412

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11856876; hg19: chr15-77973012;