Variant chr19-35125182-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139284.3(LGI4):c.*11G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,510,478 control chromosomes in the GnomAD database, including 100,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9578 hom., cov: 33)

Exomes 𝑓: 0.36 ( 91026 hom. )

Consequence

LGI4
NM_139284.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.345

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-35125182-C-T is Benign according to our data. Variant chr19-35125182-C-T is described in ClinVar as [Benign]. Clinvar id is 1221533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 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.*11G>A		3_prime_UTR_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.*11G>A		3_prime_UTR_variant	9/9	1	NM_139284.3	ENSP00000312273	P1	Q8N135-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53039

AN:

151962

Hom.:

9578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.355

AC:

64309

AN:

181168

Hom.:

12128

AF XY:

0.364

AC XY:

34770

AN XY:

95462

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.361

AC:

490786

AN:

1358398

Hom.:

91026

Cov.:

AF XY:

0.367

AC XY:

243880

AN XY:

663962

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.349

AC:

53068

AN:

152080

Hom.:

9578

Cov.:

AF XY:

0.353

AC XY:

26203

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.245

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.374

Hom.:

1349

Bravo

AF:

0.330

Asia WGS

AF:

0.387

AC:

1348

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 12, 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_noAF

Benign

-0.82

CADD

Benign

3.6

DANN

Benign

0.60

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