Variant rs61746299 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004432.4(LINGO4):c.1330A>T(p.Thr444Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,613,770 control chromosomes in the GnomAD database, including 7,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.058 ( 821 hom., cov: 33)

Exomes 𝑓: 0.035 ( 6497 hom. )

Consequence

LINGO4
NM_001004432.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Variant links:

Genes affected

LINGO4 (HGNC:31814): (leucine rich repeat and Ig domain containing 4) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LINGO4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012541711).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO4	NM_001004432.4 linkuse as main transcript	c.1330A>T	p.Thr444Ser	missense_variant	2/2	ENST00000368820.4	NP_001004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO4	ENST00000368820.4 linkuse as main transcript	c.1330A>T	p.Thr444Ser	missense_variant	2/2	1	NM_001004432.4	ENSP00000357810	P1

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8824

AN:

152078

Hom.:

823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0885

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0988

AC:

24825

AN:

251290

Hom.:

3612

AF XY:

0.0954

AC XY:

12957

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0893

Gnomad AMR exome

AF:

0.246

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00272

Gnomad OTH exome

AF:

0.0576

GnomAD4 exome

AF:

0.0349

AC:

51010

AN:

1461574

Hom.:

6497

Cov.:

AF XY:

0.0389

AC XY:

28302

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.0919

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.0455

GnomAD4 genome

AF:

0.0580

AC:

8820

AN:

152196

Hom.:

821

Cov.:

AF XY:

0.0639

AC XY:

4756

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0886

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.364

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0192

Hom.:

238

Bravo

AF:

0.0705

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.0849

AC:

374

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.0947

AC:

11494

Asia WGS

AF:

0.227

AC:

790

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.089

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.68

MutationTaster

Benign

0.85

PrimateAI

Benign

0.41

PROVEAN

Benign

0.020

REVEL

Benign

0.10

Sift

Benign

0.71

Sift4G

Benign

0.46

Polyphen

0.083

Vest4

0.042

MutPred

0.42

Gain of disorder (P = 0.0319);

MPC

0.13

ClinPred

0.010

GERP RS

5.5

Varity_R

0.049

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over