5-146114521-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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

ENSG00000251556 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020117.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS1	NM_020117.11	MANE Select	c.3326-210C>G		intron	N/A	NP_064502.9
	LARS1	NM_016460.4		c.3245-210C>G		intron	N/A	NP_057544.2
	LARS1	NM_001317964.2		c.3188-210C>G		intron	N/A	NP_001304893.1	A0A6I8PL42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS1	ENST00000394434.7	TSL:1 MANE Select	c.3326-210C>G		intron	N/A	ENSP00000377954.2	Q9P2J5-1
	LARS1	ENST00000908002.1		c.3446-210C>G		intron	N/A	ENSP00000578061.1
	LARS1	ENST00000907999.1		c.3419-210C>G		intron	N/A	ENSP00000578058.1

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

African (AFR) AF: 0.0395 AC: 1636 AN: 41394

American (AMR) AF: 0.0444 AC: 677 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5158

South Asian (SAS) AF: 0.0443 AC: 213 AN: 4804

European-Finnish (FIN) AF: 0.0541 AC: 572 AN: 10572

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4673 AN: 67938

Other (OTH) AF: 0.0602 AC: 127 AN: 2108

Alfa AF: 0.0560 Hom.: 33

Bravo AF: 0.0543

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.42
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism

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: rs116780433; hg19: chr5-145494084;