dbSNP rs11853396: LINGO1:c.*155G>C (chr15-77613889-C-G) – 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.*155G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 680,042 control chromosomes in the GnomAD database, including 48,434 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 0.39 ( 12346 hom., cov: 28)

Exomes 𝑓: 0.36 ( 36088 hom. )

Consequence

LINGO1
NM_032808.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

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: 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=-0.29).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7 link	c.*155G>C		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.*155G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_032808.7	ENSP00000347451.6		Q96FE5-1
LINGO1	ENST00000561030.5 link	c.*155G>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453853.1		Q96FE5-2

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

58865

AN:

149976

Hom.:

12329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.357

AC:

189111

AN:

529950

Hom.:

36088

Cov.:

AF XY:

0.365

AC XY:

100554

AN XY:

275378

show subpopulations

African (AFR)

AF:

0.520

AC:

7228

AN:

13894

American (AMR)

AF:

0.362

AC:

6882

AN:

19004

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

5742

AN:

14230

East Asian (EAS)

AF:

0.523

AC:

16459

AN:

31470

South Asian (SAS)

AF:

0.529

AC:

24818

AN:

46920

European-Finnish (FIN)

AF:

0.331

AC:

9791

AN:

29572

Middle Eastern (MID)

AF:

0.485

AC:

1047

AN:

2160

European-Non Finnish (NFE)

AF:

0.309

AC:

106419

AN:

344160

Other (OTH)

AF:

0.376

AC:

10725

AN:

28540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

6145

12290

18436

24581

30726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1522

3044

4566

6088

7610

<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:

0.393

AC:

58935

AN:

150092

Hom.:

12346

Cov.:

AF XY:

0.399

AC XY:

29218

AN XY:

73278

show subpopulations

African (AFR)

AF:

0.505

AC:

20534

AN:

40692

American (AMR)

AF:

0.377

AC:

5694

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1417

AN:

3454

East Asian (EAS)

AF:

0.542

AC:

2707

AN:

4998

South Asian (SAS)

AF:

0.548

AC:

2563

AN:

4674

European-Finnish (FIN)

AF:

0.349

AC:

3604

AN:

10320

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.313

AC:

21168

AN:

67580

Other (OTH)

AF:

0.393

AC:

817

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1609

3217

4826

6434

8043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.360

Hom.:

1132

Bravo

AF:

0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.1

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)

0.010

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