19-35125112-G-A

Position:

• chr19-35125112-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.*81C>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 0.353 in 1,252,094 control chromosomes in the GnomAD database, including 80,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9252 hom., cov: 33)
  • Exomes 𝑓: 0.35 (70787 hom.)
• Consequence: LGI4 NM_139284.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.496

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]

LGI4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-35125112-G-A is Benign according to our data. Variant chr19-35125112-G-A is described in ClinVar as [Benign]. Clinvar id is 1267409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI4	NM_139284.3	c.*81C>T		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	c.*81C>T		3_prime_UTR_variant	9/9	1	NM_139284.3	ENSP00000312273.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52211 AN: 152022 Hom.: 9255 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.355 AC: 390069 AN: 1099954 Hom.: 70787 Cov.: 14 AF XY: 0.360 AC XY: 195260 AN XY: 542488

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.343 AC: 52229 AN: 152140 Hom.: 9252 Cov.: 33 AF XY: 0.346 AC XY: 25754 AN XY: 74382

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.305

Alfa AF: 0.374 Hom.: 1362

Bravo AF: 0.325

Asia WGS AF: 0.347 AC: 1209 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	-0.84
CADD	Benign	6.8
DANN	Benign	0.60

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: rs1048690; hg19: chr19-35616016; COSMIC: COSV59534186; COSMIC: COSV59534186;