Genetic Variant LINGO1:c.-98-2394T>C (chr15-77679568-A-G) – 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.-98-2394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,242 control chromosomes in the GnomAD database, including 1,372 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 0.13 ( 1372 hom., cov: 32)

Consequence

LINGO1
NM_001301186.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

2 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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 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.-98-2394T>C	intron	N/A	NP_001288115.1	Q96FE5-2
LINGO1	NM_001301187.2	c.-98-2394T>C	intron	N/A	NP_001288116.1	Q96FE5-2
LINGO1	NM_001301189.2	c.-98-2394T>C	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.-98-2394T>C	intron	N/A	ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000561686.5	TSL:3	c.-13+11152T>C	intron	N/A	ENSP00000455605.1	H3BQ49
LINGO1	ENST00000567726.5	TSL:4	c.-98-2394T>C	intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19649

AN:

152124

Hom.:

1376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.155

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

GnomAD4 genome

AF:

0.129

AC:

19655

AN:

152242

Hom.:

1372

Cov.:

AF XY:

0.131

AC XY:

9727

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.108

AC:

4508

AN:

41550

American (AMR)

AF:

0.185

AC:

2833

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3468

East Asian (EAS)

AF:

0.135

AC:

699

AN:

5172

South Asian (SAS)

AF:

0.149

AC:

719

AN:

4812

European-Finnish (FIN)

AF:

0.116

AC:

1226

AN:

10614

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8321

AN:

68030

Other (OTH)

AF:

0.154

AC:

326

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

879

1758

2637

3516

4395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.142

Hom.:

366

Bravo

AF:

0.136

Asia WGS

AF:

0.150

AC:

523

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.83

(source)

DANN

Benign

0.64

PhyloP100

0.010

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