dbSNP rs3743481: LINGO1:p.Ser368Ser (chr15-77614803-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_032808.7(LINGO1):c.1104C>T(p.Ser368Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,608,936 control chromosomes in the GnomAD database, including 134,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15345 hom., cov: 33)

Exomes 𝑓: 0.40 ( 119645 hom. )

Consequence

LINGO1
NM_032808.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.50

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 15-77614803-G-A is Benign according to our data. Variant chr15-77614803-G-A is described in ClinVar as [Benign]. Clinvar id is 1300108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7 link	c.1104C>T	p.Ser368Ser	synonymous_variant	Exon 2 of 2	ENST00000355300.7	NP_116197.4	Q96FE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LINGO1	ENST00000355300.7 link	c.1104C>T	p.Ser368Ser	synonymous_variant	Exon 2 of 2	1	NM_032808.7	ENSP00000347451.6	Q96FE5-1
LINGO1	ENST00000561030.5 link	c.1086C>T	p.Ser362Ser	synonymous_variant	Exon 4 of 4	1		ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000557798.1 link	c.*141C>T		downstream_gene_variant		3		ENSP00000453780.1	H0YMX3

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67173

AN:

151988

Hom.:

15323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.430

GnomAD3 exomes

AF:

0.435

AC:

104385

AN:

240230

Hom.:

23521

AF XY:

0.441

AC XY:

57589

AN XY:

130508

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.590

Gnomad SAS exome

AF:

0.576

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.399

AC:

581507

AN:

1456830

Hom.:

119645

Cov.:

AF XY:

0.405

AC XY:

293322

AN XY:

724272

show subpopulations

Gnomad4 AFR exome

AF:

0.543

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.577

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.442

AC:

67251

AN:

152106

Hom.:

15345

Cov.:

AF XY:

0.451

AC XY:

33520

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.576

Gnomad4 SAS

AF:

0.592

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.397

Hom.:

16338

Bravo

AF:

0.437

Asia WGS

AF:

0.546

AC:

1895

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.50

CADD

Benign

8.3

DANN

Benign

0.76

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