chr3-45434501-A-G

Position:

• chr3-45434501-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015340.4(LARS2):​c.517-12390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,226 control chromosomes in the GnomAD database, including 55,551 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 0.84 (55551 hom., cov: 32)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

Genes affected

LARS2 (HGNC:17095): (leucyl-tRNA synthetase 2, mitochondrial) This gene encodes a class 1 aminoacyl-tRNA synthetase, mitochondrial leucyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.517-12390A>G		intron_variant		ENST00000645846.2	NP_056155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2	c.517-12390A>G		intron_variant			NM_015340.4	ENSP00000495093.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127193 AN: 152108 Hom.: 55524 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.836 AC: 127259 AN: 152226 Hom.: 55551 Cov.: 32 AF XY: 0.842 AC XY: 62640 AN XY: 74438

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.859

Alfa AF: 0.906 Hom.: 12912

Bravo AF: 0.812

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.2
DANN	Benign	0.86

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: rs9825041; hg19: chr3-45475993;