rs12978414

chr19-35125658-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000587780.5(LGI4):c.*510G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 736,320 control chromosomes in the GnomAD database, including 49,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9584 hom., cov: 32)
  • Exomes 𝑓: 0.36 (40169 hom.)
• Consequence: LGI4 ENST00000587780.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-35125658-C-G is Benign according to our data. Variant chr19-35125658-C-G is described in ClinVar as [Benign]. Clinvar id is 1294811.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
LGI4	NM_139284.3	c.1300-151G>C		intron_variant		ENST00000310123.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGI4	ENST00000310123.8	c.1300-151G>C		intron_variant		1	NM_139284.3	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53050 AN: 151878 Hom.: 9584 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.360 AC: 210174 AN: 584324 Hom.: 40169 Cov.: 7 AF XY: 0.372 AC XY: 115822 AN XY: 311500

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.349 AC: 53079 AN: 151996 Hom.: 9584 Cov.: 32 AF XY: 0.353 AC XY: 26218 AN XY: 74290

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.314

Alfa AF: 0.376 Hom.: 1373

Bravo AF: 0.330

Asia WGS AF: 0.387 AC: 1348 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12978414; hg19: chr19-35616562; COSMIC: COSV59533978; COSMIC: COSV59533978;