ENST00000561030.5:c.-280-2311A>G

Variant names:

• chr15-77693212-T-C
• rs12905478
• ENST00000561030.5:c.-280-2311A>G

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-280-2311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,316 control chromosomes in the GnomAD database, including 574 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 0.081 (574 hom., cov: 33)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 5 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-280-2311A>G		intron_variant	Intron 3 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-280-2311A>G		intron_variant	Intron 3 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-280-2311A>G		intron_variant	Intron 3 of 5		NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-280-2311A>G		intron_variant	Intron 1 of 3	1		ENSP00000453853.1
LINGO1	ENST00000561686.5	c.-194-2311A>G		intron_variant	Intron 2 of 3	3		ENSP00000455605.1
LINGO1	ENST00000567726.5	c.-99+14182A>G		intron_variant	Intron 1 of 2	4		ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12366 AN: 152198 Hom.: 572 Cov.: 33

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0813 AC: 12376 AN: 152316 Hom.: 574 Cov.: 33 AF XY: 0.0818 AC XY: 6093 AN XY: 74482

African (AFR) AF: 0.0487 AC: 2023 AN: 41578

American (AMR) AF: 0.0750 AC: 1147 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3470

East Asian (EAS) AF: 0.105 AC: 542 AN: 5184

South Asian (SAS) AF: 0.109 AC: 526 AN: 4826

European-Finnish (FIN) AF: 0.0791 AC: 840 AN: 10614

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0975 AC: 6636 AN: 68028

Other (OTH) AF: 0.101 AC: 213 AN: 2116

Alfa AF: 0.0913 Hom.: 572

Bravo AF: 0.0793

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.70
PhyloP100		1.4
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: rs12905478; hg19: chr15-77985554;