15-77689061-C-T

Variant names:

• chr15-77689061-C-T
• rs4886893
• ENST00000561030.5:c.-99+1659G>A

Variant summary

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

The NM_001301186.2(LINGO1):​c.-99+1659G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,014 control chromosomes in the GnomAD database, including 2,364 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 0.17 (2364 hom., cov: 33)
• Consequence: LINGO1 NM_001301186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_001301186.2		c.-99+1659G>A		intron	N/A	NP_001288115.1
	LINGO1	NM_001301187.2		c.-99+1659G>A		intron	N/A	NP_001288116.1
	LINGO1	NM_001301189.2		c.-99+1659G>A		intron	N/A	NP_001288118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000561030.5	TSL:1	c.-99+1659G>A		intron	N/A	ENSP00000453853.1
	LINGO1	ENST00000561686.5	TSL:3	c.-13+1659G>A		intron	N/A	ENSP00000455605.1
	LINGO1	ENST00000567726.5	TSL:4	c.-98-11887G>A		intron	N/A	ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26185 AN: 151896 Hom.: 2366 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.172 AC: 26195 AN: 152014 Hom.: 2364 Cov.: 33 AF XY: 0.173 AC XY: 12817 AN XY: 74300

African (AFR) AF: 0.112 AC: 4632 AN: 41446

American (AMR) AF: 0.218 AC: 3334 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3466

East Asian (EAS) AF: 0.116 AC: 596 AN: 5158

South Asian (SAS) AF: 0.166 AC: 796 AN: 4802

European-Finnish (FIN) AF: 0.179 AC: 1889 AN: 10566

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13560 AN: 67990

Other (OTH) AF: 0.191 AC: 401 AN: 2104

Alfa AF: 0.188 Hom.: 3390

Bravo AF: 0.174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		-0.081
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: rs4886893; hg19: chr15-77981403;