Variant 19-35125183-G-A 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.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,510,940 control chromosomes in the GnomAD database, including 53,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4407 hom., cov: 33)

Exomes 𝑓: 0.26 ( 48979 hom. )

Consequence

LGI4
NM_139284.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-35125183-G-A is Benign according to our data. Variant chr19-35125183-G-A is described in ClinVar as [Benign]. Clinvar id is 1247836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) 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
LGI4	NM_139284.3 linkuse as main transcript	c.*10C>T		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.*10C>T		3_prime_UTR_variant	9/9	1	NM_139284.3	ENSP00000312273	P1	Q8N135-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33969

AN:

152114

Hom.:

4395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.266

AC:

48244

AN:

181386

Hom.:

7343

AF XY:

0.259

AC XY:

24791

AN XY:

95628

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.262

AC:

355487

AN:

1358708

Hom.:

48979

Cov.:

AF XY:

0.258

AC XY:

171516

AN XY:

664234

show subpopulations

Gnomad4 AFR exome

AF:

0.0946

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.223

AC:

33995

AN:

152232

Hom.:

4407

Cov.:

AF XY:

0.227

AC XY:

16871

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.228

Hom.:

1340

Bravo

AF:

0.230

Asia WGS

AF:

0.217

AC:

757

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

-0.91

CADD

Benign

0.069

DANN

Benign

0.68

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