15-77689061-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001301186.2(LINGO1):​c.-99+1659G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 152,056 control chromosomes in the GnomAD database, including 3 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 0.0029 (3 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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.-99+1659G>C		intron	N/A	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.-99+1659G>C		intron	N/A	NP_001288116.1	Q96FE5-2
	LINGO1	NM_001301189.2		c.-99+1659G>C		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.-99+1659G>C		intron	N/A	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000561686.5	TSL:3	c.-13+1659G>C		intron	N/A	ENSP00000455605.1	H3BQ49
	LINGO1	ENST00000567726.5	TSL:4	c.-98-11887G>C		intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 433 AN: 151938 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000960

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

GnomAD4 genome AF: 0.00286 AC: 435 AN: 152056 Hom.: 3 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74320

African (AFR) AF: 0.0103 AC: 427 AN: 41454

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00 Hom.: 3390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		-0.081
Mutation Taster		=100/0	polymorphism

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;