19-35125091-C-T

Position:

• chr19-35125091-C-T

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.*102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,008,976 control chromosomes in the GnomAD database, including 64,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9594 hom., cov: 33)
  • Exomes 𝑓: 0.35 (55319 hom.)
• Consequence: LGI4 NM_139284.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.08

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=-0.82).
• BP6: Variant 19-35125091-C-T is Benign according to our data. Variant chr19-35125091-C-T is described in ClinVar as [Benign]. Clinvar id is 1272831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI4	NM_139284.3	c.*102G>A		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	c.*102G>A		3_prime_UTR_variant	9/9	1	NM_139284.3	ENSP00000312273	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53095 AN: 152038 Hom.: 9594 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.354 AC: 303134 AN: 856820 Hom.: 55319 Cov.: 11 AF XY: 0.360 AC XY: 154003 AN XY: 427672

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.349 AC: 53124 AN: 152156 Hom.: 9594 Cov.: 33 AF XY: 0.353 AC XY: 26253 AN XY: 74380

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.314

Alfa AF: 0.340 Hom.: 11084

Bravo AF: 0.330

Asia WGS AF: 0.388 AC: 1349 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	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.74

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: rs14358; hg19: chr19-35615995; COSMIC: COSV59534183; COSMIC: COSV59534183;