Variant 15-77614797-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032808.7(LINGO1):c.1110G>A(p.Pro370Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,610,034 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 6 hom., cov: 33)

Exomes 𝑓: 0.013 ( 162 hom. )

Consequence

LINGO1
NM_032808.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.75

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-77614797-C-T is Benign according to our data. Variant chr15-77614797-C-T is described in ClinVar as [Benign]. Clinvar id is 771195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_032808.7 linkuse as main transcript	c.1110G>A	p.Pro370Pro	synonymous_variant	2/2	ENST00000355300.7	NP_116197.4	Q96FE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7 linkuse as main transcript	c.1110G>A	p.Pro370Pro	synonymous_variant	2/2	1	NM_032808.7	ENSP00000347451.6		Q96FE5-1
LINGO1	ENST00000561030.5 linkuse as main transcript	c.1092G>A	p.Pro364Pro	synonymous_variant	4/4	1		ENSP00000453853.1		Q96FE5-2

Frequencies

GnomAD3 genomes

AF:

0.00819

AC:

1246

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00811

AC:

1950

AN:

240436

Hom.:

AF XY:

0.00814

AC XY:

1063

AN XY:

130566

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00538

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00244

Gnomad FIN exome

AF:

0.00624

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00933

GnomAD4 exome

AF:

0.0130

AC:

18908

AN:

1457690

Hom.:

162

Cov.:

AF XY:

0.0126

AC XY:

9125

AN XY:

724738

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00295

Gnomad4 FIN exome

AF:

0.00597

Gnomad4 NFE exome

AF:

0.0152

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.00818

AC:

1246

AN:

152344

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

559

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00902

Hom.:

Bravo

AF:

0.00844

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	LINGO1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

DANN

Benign

0.79

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