Variant rs111605415 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_032808.7(LINGO1):c.1610G>C(p.Gly537Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

LINGO1
NM_032808.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, LINGO1

BP4

Computational evidence support a benign effect (MetaRNN=0.020240009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7 linkuse as main transcript	c.1610G>C	p.Gly537Ala	missense_variant	2/2	ENST00000355300.7
LOC105370906	XR_001751806.2 linkuse as main transcript	n.689-15988C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7 linkuse as main transcript	c.1610G>C	p.Gly537Ala	missense_variant	2/2	1	NM_032808.7	A1	Q96FE5-1
LINGO1	ENST00000561030.5 linkuse as main transcript	c.1592G>C	p.Gly531Ala	missense_variant	4/4	1		P4	Q96FE5-2

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000518

AC:

129

AN:

249030

Hom.:

AF XY:

0.000437

AC XY:

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000895

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.00108

AC:

1576

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

730

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000558

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000962

Hom.:

Bravo

AF:

0.000586

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00106

AC:

ExAC

AF:

0.000421

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

Cadd

Uncertain

Dann

Benign

0.91

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.0035

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

0.75

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.092

Sift

Benign

0.39

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;.

Vest4

0.081

MVP

0.13

MPC

0.86

ClinPred

0.012

GERP RS

4.2

Varity_R

0.060

gMVP

0.67

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over