Variant 15-77615433-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032808.7(LINGO1):c.474A>G(p.Leu158Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,144 control chromosomes in the GnomAD database, including 337,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 32713 hom., cov: 33)

Exomes 𝑓: 0.64 ( 304429 hom. )

Consequence

LINGO1
NM_032808.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.641

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 15-77615433-T-C is Benign according to our data. Variant chr15-77615433-T-C is described in ClinVar as [Benign]. Clinvar id is 1270589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.641 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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.474A>G	p.Leu158Leu	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.474A>G	p.Leu158Leu	synonymous_variant	2/2	1	NM_032808.7	ENSP00000347451.6	Q96FE5-1
LINGO1	ENST00000561030.5 linkuse as main transcript	c.456A>G	p.Leu152Leu	synonymous_variant	4/4	1		ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000557798.1 linkuse as main transcript	c.489A>G	p.Leu163Leu	synonymous_variant	2/2	3		ENSP00000453780.1	H0YMX3
LINGO1	ENST00000561686.5 linkuse as main transcript	c.456A>G	p.Leu152Leu	synonymous_variant	4/4	3		ENSP00000455605.1	H3BQ49

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99424

AN:

151550

Hom.:

32682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.652

GnomAD3 exomes

AF:

0.668

AC:

166487

AN:

249156

Hom.:

56183

AF XY:

0.675

AC XY:

91203

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.803

Gnomad SAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.662

GnomAD4 exome

AF:

0.643

AC:

939807

AN:

1461474

Hom.:

304429

Cov.:

AF XY:

0.648

AC XY:

471195

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.685

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.656

AC:

99507

AN:

151670

Hom.:

32713

Cov.:

AF XY:

0.662

AC XY:

49039

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.671

Gnomad4 AMR

AF:

0.653

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.790

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.633

Hom.:

59359

Bravo

AF:

0.653

Asia WGS

AF:

0.738

AC:

2563

AN:

3476

EpiCase

AF:

0.638

EpiControl

AF:

0.637

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

-0.54

CADD

Benign

DANN

Benign

0.71

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