3-45391775-C-G

Position:

• chr3-45391775-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015340.4(LARS2):​c.-22+127C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,220 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (179 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-45391775-C-G is Benign according to our data. Variant chr3-45391775-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1207282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.-22+127C>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.-22+127C>G		intron_variant			NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6916 AN: 152102 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.0393

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

GnomAD4 genome AF: 0.0455 AC: 6923 AN: 152220 Hom.: 179 Cov.: 32 AF XY: 0.0448 AC XY: 3334 AN XY: 74456

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0400

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0472 Hom.: 21

Bravo AF: 0.0446

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.53

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: rs78674974; hg19: chr3-45433267;