19-35126049-T-C

Position:

• chr19-35126049-T-C

Variant summary

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

The ENST00000587780.5(LGI4):​c.*119A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 600,492 control chromosomes in the GnomAD database, including 41,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9592 hom., cov: 32)
  • Exomes 𝑓: 0.37 (32322 hom.)
• Consequence: LGI4 ENST00000587780.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.139

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=-0.85).
• BP6: Variant 19-35126049-T-C is Benign according to our data. Variant chr19-35126049-T-C is described in ClinVar as [Benign]. Clinvar id is 1277858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI4	NM_139284.3	c.1299+221A>G		intron_variant		ENST00000310123.8	NP_644813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI4	ENST00000310123.8	c.1299+221A>G		intron_variant		1	NM_139284.3	ENSP00000312273	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53051 AN: 151696 Hom.: 9592 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.370 AC: 166071 AN: 448678 Hom.: 32322 Cov.: 4 AF XY: 0.383 AC XY: 90290 AN XY: 235694

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.350 AC: 53080 AN: 151814 Hom.: 9592 Cov.: 32 AF XY: 0.353 AC XY: 26210 AN XY: 74160

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.315

Alfa AF: 0.368 Hom.: 1147

Bravo AF: 0.330

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1632457; hg19: chr19-35616953;