Genetic Variant LINGO1:c.*182A>G (chr15-77613862-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_032808.7(LINGO1):c.*182A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 613,578 control chromosomes in the GnomAD database, including 31,389 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 0.30 ( 6722 hom., cov: 30)

Exomes 𝑓: 0.32 ( 24667 hom. )

Consequence

LINGO1
NM_032808.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

18 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LINGO1 links:

LOC105370906 (HGNC:):

LOC105370906 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7 link	c.*182A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000355300.7	NP_116197.4	Q96FE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7 link	c.*182A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_032808.7	ENSP00000347451.6		Q96FE5-1
LINGO1	ENST00000561030.5 link	c.*182A>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453853.1		Q96FE5-2

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

43867

AN:

146624

Hom.:

6722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.216

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.320

AC:

149449

AN:

466850

Hom.:

24667

Cov.:

AF XY:

0.316

AC XY:

77148

AN XY:

244412

show subpopulations

African (AFR)

AF:

0.195

AC:

2489

AN:

12758

American (AMR)

AF:

0.356

AC:

6592

AN:

18530

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

3030

AN:

13764

East Asian (EAS)

AF:

0.304

AC:

9447

AN:

31072

South Asian (SAS)

AF:

0.240

AC:

10689

AN:

44594

European-Finnish (FIN)

AF:

0.335

AC:

9833

AN:

29322

Middle Eastern (MID)

AF:

0.219

AC:

443

AN:

2022

European-Non Finnish (NFE)

AF:

0.344

AC:

99020

AN:

288200

Other (OTH)

AF:

0.297

AC:

7906

AN:

26588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5226

10452

15677

20903

26129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

43882

AN:

146728

Hom.:

6722

Cov.:

AF XY:

0.297

AC XY:

21262

AN XY:

71484

show subpopulations

African (AFR)

AF:

0.216

AC:

8479

AN:

39192

American (AMR)

AF:

0.332

AC:

4903

AN:

14774

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

788

AN:

3438

East Asian (EAS)

AF:

0.274

AC:

1306

AN:

4764

South Asian (SAS)

AF:

0.244

AC:

1085

AN:

4450

European-Finnish (FIN)

AF:

0.341

AC:

3352

AN:

9830

Middle Eastern (MID)

AF:

0.212

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.343

AC:

23004

AN:

67046

Other (OTH)

AF:

0.294

AC:

602

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

1495

2990

4485

5980

7475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.314

Hom.:

9813

Bravo

AF:

0.288

Asia WGS

AF:

0.219

AC:

762

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over