15-77692138-C-T

Variant names:

• chr15-77692138-C-T
• rs4243047
• ENST00000561030.5:c.-280-1237G>A

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-280-1237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,058 control chromosomes in the GnomAD database, including 14,758 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 0.42 (14758 hom., cov: 33)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-280-1237G>A		intron_variant	Intron 3 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-280-1237G>A		intron_variant	Intron 3 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-280-1237G>A		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.-280-1237G>A		intron_variant	Intron 1 of 3	1		ENSP00000453853.1
LINGO1	ENST00000561686.5	c.-194-1237G>A		intron_variant	Intron 2 of 3	3		ENSP00000455605.1
LINGO1	ENST00000567726.5	c.-98-14964G>A		intron_variant	Intron 1 of 2	4		ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64215 AN: 151938 Hom.: 14736 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.423 AC: 64292 AN: 152058 Hom.: 14758 Cov.: 33 AF XY: 0.421 AC XY: 31300 AN XY: 74326

African (AFR) AF: 0.616 AC: 25528 AN: 41458

American (AMR) AF: 0.360 AC: 5494 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1378 AN: 3466

East Asian (EAS) AF: 0.391 AC: 2017 AN: 5156

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3205 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23479 AN: 67984

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.371 Hom.: 34031

Bravo AF: 0.435

Asia WGS AF: 0.428 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.58
DANN	Benign	0.59
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: rs4243047; hg19: chr15-77984480;