Variant 19-35125412-C-T 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_139284.3(LGI4):c.1395G>A(p.Gln465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,608,378 control chromosomes in the GnomAD database, including 107,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9415 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98584 hom. )

Consequence

LGI4
NM_139284.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

LGI4 (HGNC:18712): (leucine rich repeat LGI family member 4) Involved in regulation of myelination. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in arthrogryposis multiplex congenita-1 and childhood absence epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

LGI4 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 (MetaRNN=2.2032857E-4).

BP6

Variant 19-35125412-C-T is Benign according to our data. Variant chr19-35125412-C-T is described in ClinVar as [Benign]. Clinvar id is 1272294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI4	NM_139284.3 linkuse as main transcript	c.1395G>A	p.Gln465=	synonymous_variant	9/9	ENST00000310123.8	NP_644813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI4	ENST00000310123.8 linkuse as main transcript	c.1395G>A	p.Gln465=	synonymous_variant	9/9	1	NM_139284.3	ENSP00000312273	P1	Q8N135-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52724

AN:

151596

Hom.:

9415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.312

GnomAD3 exomes

AF:

0.364

AC:

87702

AN:

241074

Hom.:

16671

AF XY:

0.378

AC XY:

49333

AN XY:

130680

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.363

AC:

528644

AN:

1456664

Hom.:

98584

Cov.:

AF XY:

0.370

AC XY:

268012

AN XY:

724114

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.348

AC:

52753

AN:

151714

Hom.:

9415

Cov.:

AF XY:

0.351

AC XY:

26001

AN XY:

74090

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.358

Hom.:

5425

Bravo

AF:

0.330

TwinsUK

AF:

0.351

AC:

1303

ALSPAC

AF:

0.357

AC:

1374

ESP6500AA

AF:

0.329

AC:

1450

ESP6500EA

AF:

0.355

AC:

3054

ExAC

AF:

0.359

AC:

43559

Asia WGS

AF:

0.387

AC:

1345

AN:

3478

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	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect

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_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.97

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.29

MetaRNN

Benign

0.00022

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.95

P;P;P

PROVEAN

Benign

-0.13

REVEL

Benign

0.090

Sift

Pathogenic

0.0

Vest4

0.057

ClinPred

0.048

GERP RS

5.1

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