19-35125641-G-A

Position:

• chr19-35125641-G-A

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.*527C>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 0.00663 in 799,638 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (32 hom.)
• Consequence: LGI4 ENST00000587780.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.344

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 19-35125641-G-A is Benign according to our data. Variant chr19-35125641-G-A is described in ClinVar as [Benign]. Clinvar id is 1281124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI4	NM_139284.3	c.1300-134C>T		intron_variant		ENST00000310123.8	NP_644813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI4	ENST00000310123.8	c.1300-134C>T		intron_variant		1	NM_139284.3	ENSP00000312273	P1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3200 AN: 152096 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00324 AC: 2097 AN: 647424 Hom.: 32 Cov.: 8 AF XY: 0.00281 AC XY: 954 AN XY: 339018

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.00518

Gnomad4 ASJ exome AF: 0.000429

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000544

Gnomad4 FIN exome AF: 0.0000284

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.00671

GnomAD4 genome AF: 0.0211 AC: 3205 AN: 152214 Hom.: 103 Cov.: 32 AF XY: 0.0205 AC XY: 1523 AN XY: 74426

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0252 Hom.: 8

Bravo AF: 0.0253

Asia WGS AF: 0.00404 AC: 15 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 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
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: rs58799071; hg19: chr19-35616545;