Genetic Variant LINGO1:c.-280-559A>G (chr15-77691460-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001301186.2(LINGO1):c.-280-559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,776 control chromosomes in the GnomAD database, including 24,643 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 0.57 ( 24643 hom., cov: 31)

Consequence

LINGO1
NM_001301186.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

7 publications found

Variant links:

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)

LINGO1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO1	NM_001301186.2	c.-280-559A>G	intron	N/A	NP_001288115.1	Q96FE5-2
LINGO1	NM_001301187.2	c.-280-559A>G	intron	N/A	NP_001288116.1	Q96FE5-2
LINGO1	NM_001301189.2	c.-280-559A>G	intron	N/A	NP_001288118.1	Q96FE5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO1	ENST00000561030.5	TSL:1	c.-280-559A>G	intron	N/A	ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000561686.5	TSL:3	c.-194-559A>G	intron	N/A	ENSP00000455605.1	H3BQ49
LINGO1	ENST00000567726.5	TSL:4	c.-98-14286A>G	intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85862

AN:

151658

Hom.:

24621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.583

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

GnomAD4 genome

AF:

0.566

AC:

85942

AN:

151776

Hom.:

24643

Cov.:

AF XY:

0.564

AC XY:

41841

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.655

AC:

27098

AN:

41392

American (AMR)

AF:

0.521

AC:

7951

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2124

AN:

3468

East Asian (EAS)

AF:

0.432

AC:

2194

AN:

5080

South Asian (SAS)

AF:

0.520

AC:

2497

AN:

4802

European-Finnish (FIN)

AF:

0.507

AC:

5354

AN:

10550

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.543

AC:

36884

AN:

67906

Other (OTH)

AF:

0.581

AC:

1226

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3712

5568

7424

9280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.548

Hom.:

41600

Bravo

AF:

0.573

Asia WGS

AF:

0.524

AC:

1824

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.55

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over