5-146114521-G-C

Variant names:

• chr5-146114521-G-C
• rs116780433
• NM_020117.11:c.3326-210C>G

Variant summary

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

The NM_020117.11(LARS1):​c.3326-210C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 151,898 control chromosomes in the GnomAD database, including 279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.055 (279 hom., cov: 31)
• Consequence: LARS1 NM_020117.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110

Genes affected

LARS1 (HGNC:6512): (leucyl-tRNA synthetase 1) This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]

ENSG00000251556 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 5-146114521-G-C is Benign according to our data. Variant chr5-146114521-G-C is described in ClinVar as [Benign]. Clinvar id is 684235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS1	NM_020117.11	c.3326-210C>G		intron_variant	Intron 31 of 31	ENST00000394434.7	NP_064502.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARS1	ENST00000394434.7	c.3326-210C>G		intron_variant	Intron 31 of 31	1	NM_020117.11	ENSP00000377954.2

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8382 AN: 151780 Hom.: 279 Cov.: 31

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0552 AC: 8381 AN: 151898 Hom.: 279 Cov.: 31 AF XY: 0.0532 AC XY: 3952 AN XY: 74226

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0602

Alfa AF: 0.0560 Hom.: 33

Bravo AF: 0.0543

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.42

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: rs116780433; hg19: chr5-145494084;