5-146145585-T-C

Variant names:

• chr5-146145585-T-C
• rs1054020
• NM_020117.11:c.1504-876A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020117.11(LARS1):​c.1504-876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,052 control chromosomes in the GnomAD database, including 28,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28038 hom., cov: 32)
• Consequence: LARS1 NM_020117.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 3 publications found

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]

LARS1 Gene-Disease associations (from GenCC):

• infantile liver failure syndrome 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS1	NM_020117.11	c.1504-876A>G		intron_variant	Intron 15 of 31	ENST00000394434.7	NP_064502.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARS1	ENST00000394434.7	c.1504-876A>G		intron_variant	Intron 15 of 31	1	NM_020117.11	ENSP00000377954.2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91240 AN: 151934 Hom.: 28028 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.600 AC: 91263 AN: 152052 Hom.: 28038 Cov.: 32 AF XY: 0.605 AC XY: 44993 AN XY: 74340

African (AFR) AF: 0.491 AC: 20342 AN: 41462

American (AMR) AF: 0.571 AC: 8707 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3470

East Asian (EAS) AF: 0.786 AC: 4077 AN: 5190

South Asian (SAS) AF: 0.780 AC: 3757 AN: 4818

European-Finnish (FIN) AF: 0.628 AC: 6633 AN: 10568

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43325 AN: 67976

Other (OTH) AF: 0.630 AC: 1329 AN: 2110

Alfa AF: 0.619 Hom.: 3701

Bravo AF: 0.586

Asia WGS AF: 0.762 AC: 2634 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		-0.73
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

Other links and lift over

dbSNP: rs1054020; hg19: chr5-145525148;