3-45546491-A-G

Position:

• chr3-45546491-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.2533-860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,220 control chromosomes in the GnomAD database, including 5,906 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 0.27 (5906 hom., cov: 32)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.2533-860A>G		intron_variant		ENST00000645846.2	NP_056155.1
LARS2	NM_001368263.1	c.2533-860A>G		intron_variant			NP_001355192.1
LARS2	XM_017006042.2	c.2405-860A>G		intron_variant			XP_016861531.1
LARS2	XM_047447830.1	c.2405-860A>G		intron_variant			XP_047303786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2	c.2533-860A>G		intron_variant			NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41303 AN: 152100 Hom.: 5902 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.271 AC: 41316 AN: 152220 Hom.: 5906 Cov.: 32 AF XY: 0.267 AC XY: 19869 AN XY: 74412

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.312

Alfa AF: 0.276 Hom.: 987

Bravo AF: 0.275

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.35

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: rs3821895; hg19: chr3-45587983;