19-35125183-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.69

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]

ACMG classification

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	UniProt
LGI4	NM_139284.3	c.*10C>T		3_prime_UTR_variant	9/9	ENST00000310123.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGI4	ENST00000310123.8	c.*10C>T		3_prime_UTR_variant	9/9	1	NM_139284.3	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33969 AN: 152114 Hom.: 4395 Cov.: 33

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

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.: 37 AF XY: 0.258 AC XY: 171516 AN XY: 664234

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.: 33 AF XY: 0.227 AC XY: 16871 AN XY: 74420

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs3826989; hg19: chr19-35616087; COSMIC: COSV59532885; COSMIC: COSV59532885;