dbSNP rs2271398: LINGO1:p.Ile155Ile (chr15-77615442-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032808.7(LINGO1):c.465C>T(p.Ile155Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,613,138 control chromosomes in the GnomAD database, including 335,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32515 hom., cov: 33)

Exomes 𝑓: 0.64 ( 302909 hom. )

Consequence

LINGO1
NM_032808.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.436

Publications

22 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 15-77615442-G-A is Benign according to our data. Variant chr15-77615442-G-A is described in ClinVar as Benign. ClinVar VariationId is 1248197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.436 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7 link	c.465C>T	p.Ile155Ile	synonymous_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.465C>T	p.Ile155Ile	synonymous_variant	Exon 2 of 2	1	NM_032808.7	ENSP00000347451.6		Q96FE5-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99155

AN:

151566

Hom.:

32486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.789

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.652

GnomAD2 exomes

AF:

0.666

AC:

165846

AN:

249108

AF XY:

0.672

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.783

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.660

GnomAD4 exome

AF:

0.642

AC:

937627

AN:

1461452

Hom.:

302909

Cov.:

AF XY:

0.647

AC XY:

470088

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.683

AC:

22875

AN:

33478

American (AMR)

AF:

0.626

AC:

28003

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

16204

AN:

26134

East Asian (EAS)

AF:

0.782

AC:

31053

AN:

39696

South Asian (SAS)

AF:

0.778

AC:

67091

AN:

86258

European-Finnish (FIN)

AF:

0.665

AC:

35479

AN:

53374

Middle Eastern (MID)

AF:

0.671

AC:

3865

AN:

5764

European-Non Finnish (NFE)

AF:

0.624

AC:

694062

AN:

1111668

Other (OTH)

AF:

0.646

AC:

38995

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

20538

41076

61615

82153

102691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18618

37236

55854

74472

93090

<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:

0.654

AC:

99236

AN:

151686

Hom.:

32515

Cov.:

AF XY:

0.660

AC XY:

48919

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.670

AC:

27691

AN:

41338

American (AMR)

AF:

0.652

AC:

9945

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2151

AN:

3464

East Asian (EAS)

AF:

0.773

AC:

3960

AN:

5126

South Asian (SAS)

AF:

0.789

AC:

3797

AN:

4812

European-Finnish (FIN)

AF:

0.667

AC:

7039

AN:

10554

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.627

AC:

42514

AN:

67818

Other (OTH)

AF:

0.651

AC:

1374

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1821

3642

5463

7284

9105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.638

Hom.:

16654

Bravo

AF:

0.651

Asia WGS

AF:

0.729

AC:

2533

AN:

3476

EpiCase

AF:

0.638

EpiControl

AF:

0.636

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability, autosomal recessive 64

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.3

(source)

DANN

Benign

0.83

PhyloP100

0.44

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over