19-35125182-C-T

Variant names:

• chr19-35125182-C-T
• rs11084800
• NM_139284.3:c.*11G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139284.3(LGI4):​c.*11G>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 0.36 in 1,510,478 control chromosomes in the GnomAD database, including 100,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9578 hom., cov: 33)
  • Exomes 𝑓: 0.36 (91026 hom.)
• Consequence: LGI4 NM_139284.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.345

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-35125182-C-T is Benign according to our data. Variant chr19-35125182-C-T is described in ClinVar as [Benign]. Clinvar id is 1221533.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 rank	MANE	Protein	UniProt
LGI4	NM_139284.3	c.*11G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000310123.8	NP_644813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI4	ENST00000310123	c.*11G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_139284.3	ENSP00000312273.3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53039 AN: 151962 Hom.: 9578 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: 0.382

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.355 AC: 64309 AN: 181168 AF XY: 0.364

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.361 AC: 490786 AN: 1358398 Hom.: 91026 Cov.: 31 AF XY: 0.367 AC XY: 243880 AN XY: 663962

Gnomad4 AFR exome AF: 0.323 AC: 9773 AN: 30244

Gnomad4 AMR exome AF: 0.261 AC: 7858 AN: 30126

Gnomad4 ASJ exome AF: 0.390 AC: 7762 AN: 19926

Gnomad4 EAS exome AF: 0.237 AC: 9130 AN: 38528

Gnomad4 SAS exome AF: 0.558 AC: 39147 AN: 70094

Gnomad4 FIN exome AF: 0.405 AC: 19976 AN: 49360

Gnomad4 NFE exome AF: 0.354 AC: 374948 AN: 1059084

Gnomad4 Remaining exome AF: 0.362 AC: 20192 AN: 55740

GnomAD4 genome AF: 0.349 AC: 53068 AN: 152080 Hom.: 9578 Cov.: 33 AF XY: 0.353 AC XY: 26203 AN XY: 74320

Gnomad4 AFR AF: 0.332 AC: 0.331838 AN: 0.331838

Gnomad4 AMR AF: 0.278 AC: 0.27804 AN: 0.27804

Gnomad4 ASJ AF: 0.394 AC: 0.393721 AN: 0.393721

Gnomad4 EAS AF: 0.245 AC: 0.244776 AN: 0.244776

Gnomad4 SAS AF: 0.544 AC: 0.543929 AN: 0.543929

Gnomad4 FIN AF: 0.402 AC: 0.401703 AN: 0.401703

Gnomad4 NFE AF: 0.361 AC: 0.36073 AN: 0.36073

Gnomad4 OTH AF: 0.314 AC: 0.314218 AN: 0.314218

Alfa AF: 0.360 Hom.: 2657

Bravo AF: 0.330

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs11084800; hg19: chr19-35616086; COSMIC: COSV59534193; COSMIC: COSV59534193;