rs13313467

Variant names:

• chr15-77673826-C-A
• rs13313467
• ENST00000561030.5:c.-13+3263G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301186.2(LINGO1):​c.-13+3263G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,922 control chromosomes in the GnomAD database, including 6,454 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 0.27 (6454 hom., cov: 32)
• Consequence: LINGO1 NM_001301186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 3 publications found

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]

LINGO1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 64

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301186.2. 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
	LINGO1	NM_001301186.2		c.-13+3263G>T		intron	N/A	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.-13+3263G>T		intron	N/A	NP_001288116.1	Q96FE5-2
	LINGO1	NM_001301189.2		c.-13+3263G>T		intron	N/A	NP_001288118.1	Q96FE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000561030.5	TSL:1	c.-13+3263G>T		intron	N/A	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000561686.5	TSL:3	c.-13+16894G>T		intron	N/A	ENSP00000455605.1	H3BQ49
	LINGO1	ENST00000567726.5	TSL:4	c.-13+3263G>T		intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41156 AN: 151804 Hom.: 6442 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.271 AC: 41208 AN: 151922 Hom.: 6454 Cov.: 32 AF XY: 0.271 AC XY: 20096 AN XY: 74244

African (AFR) AF: 0.430 AC: 17789 AN: 41372

American (AMR) AF: 0.165 AC: 2517 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1256 AN: 5164

South Asian (SAS) AF: 0.201 AC: 969 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2316 AN: 10544

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14845 AN: 67970

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.252 Hom.: 1073

Bravo AF: 0.272

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.038
DANN	Benign	0.39
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13313467; hg19: chr15-77966168;