19-35126218-A-G

Position:

• chr19-35126218-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The ENST00000587780.5(LGI4):​c.1087T>C​(p.Leu363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,580,818 control chromosomes in the GnomAD database, including 104,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9267 hom., cov: 31)
  • Exomes 𝑓: 0.36 (94819 hom.)
• Consequence: LGI4 ENST00000587780.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.153

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-35126218-A-G is Benign according to our data. Variant chr19-35126218-A-G is described in ClinVar as [Benign]. Clinvar id is 1266397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGI4	NM_139284.3	c.1299+52T>C		intron_variant		ENST00000310123.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGI4	ENST00000310123.8	c.1299+52T>C		intron_variant		1	NM_139284.3	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52234 AN: 151734 Hom.: 9270 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.309

GnomAD3 exomes AF: 0.357 AC: 76824 AN: 215126 Hom.: 14429 AF XY: 0.370 AC XY: 43032 AN XY: 116326

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.532

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.360 AC: 514543 AN: 1428968 Hom.: 94819 Cov.: 29 AF XY: 0.366 AC XY: 259330 AN XY: 708038

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.344 AC: 52253 AN: 151850 Hom.: 9267 Cov.: 31 AF XY: 0.347 AC XY: 25751 AN XY: 74218

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.306

Alfa AF: 0.365 Hom.: 2119

Bravo AF: 0.326

Asia WGS AF: 0.348 AC: 1211 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.73

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: rs937087; hg19: chr19-35617122;