Variant chr19-35125411-G-A 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.1396C>T(p.Leu466=) 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 1,608,600 control chromosomes in the GnomAD database, including 107,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9413 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98583 hom. )

Consequence

LGI4
NM_139284.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.12

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 (BayesDel_noAF=-0.55).

BP6

Variant 19-35125411-G-A is Benign according to our data. Variant chr19-35125411-G-A is described in ClinVar as [Benign]. Clinvar id is 1243576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 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.1396C>T	p.Leu466=	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.1396C>T	p.Leu466=	synonymous_variant	9/9	1	NM_139284.3	ENSP00000312273	P1	Q8N135-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52716

AN:

151638

Hom.:

9413

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:

0.543

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.312

GnomAD3 exomes

AF:

0.363

AC:

87675

AN:

241300

Hom.:

16656

AF XY:

0.377

AC XY:

49320

AN XY:

130766

show subpopulations

Gnomad AFR exome

AF:

0.325

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.363

AC:

528639

AN:

1456844

Hom.:

98583

Cov.:

AF XY:

0.370

AC XY:

268015

AN XY:

724218

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:

0.559

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.348

AC:

52745

AN:

151756

Hom.:

9413

Cov.:

AF XY:

0.351

AC XY:

25996

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.358

Hom.:

4630

Bravo

AF:

0.330

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

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_noAF

Benign

-0.55

CADD

Benign

7.6

DANN

Benign

0.94

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