Variant rs2271398 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

LOC105370906 (HGNC:):

LOC105370906 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
LINGO1	NM_032808.7 linkuse as main transcript	c.465C>T	p.Ile155Ile	synonymous_variant	2/2	ENST00000355300.7	NP_116197.4	Q96FE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LINGO1	ENST00000355300.7 linkuse as main transcript	c.465C>T	p.Ile155Ile	synonymous_variant	2/2	1	NM_032808.7	ENSP00000347451.6	Q96FE5-1
LINGO1	ENST00000561030.5 linkuse as main transcript	c.447C>T	p.Ile149Ile	synonymous_variant	4/4	1		ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000557798.1 linkuse as main transcript	c.480C>T	p.Ile160Ile	synonymous_variant	2/2	3		ENSP00000453780.1	H0YMX3
LINGO1	ENST00000561686.5 linkuse as main transcript	c.447C>T	p.Ile149Ile	synonymous_variant	4/4	3		ENSP00000455605.1	H3BQ49

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

GnomAD3 exomes

AF:

0.666

AC:

165846

AN:

249108

Hom.:

55698

AF XY:

0.672

AC XY:

90869

AN XY:

135148

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 SAS exome

AF:

0.773

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

Gnomad4 AFR exome

AF:

0.683

Gnomad4 AMR exome

AF:

0.626

Gnomad4 ASJ exome

AF:

0.620

Gnomad4 EAS exome

AF:

0.782

Gnomad4 SAS exome

AF:

0.778

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.624

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.654

AC:

99236

AN:

151686

Hom.:

32515

Cov.:

AF XY:

0.660

AC XY:

48919

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.621

Gnomad4 EAS

AF:

0.773

Gnomad4 SAS

AF:

0.789

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.627

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.637

Hom.:

16469

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -

Intellectual disability, autosomal recessive 64

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.3

DANN

Benign

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over