3-45388753-C-G

Position:

• chr3-45388753-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.-88+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,350 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2680 hom., cov: 32)
  • Exomes 𝑓: 0.24 (9 hom.)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.247

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=-0.78).
• BP6: Variant 3-45388753-C-G is Benign according to our data. Variant chr3-45388753-C-G is described in ClinVar as [Benign]. Clinvar id is 1248620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.-88+73C>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.-88+73C>G		intron_variant			NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28075 AN: 152020 Hom.: 2672 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00675

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.241 AC: 51 AN: 212 Hom.: 9 Cov.: 0 AF XY: 0.256 AC XY: 41 AN XY: 160

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.185 AC: 28107 AN: 152138 Hom.: 2680 Cov.: 32 AF XY: 0.179 AC XY: 13283 AN XY: 74398

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.181

Alfa AF: 0.108 Hom.: 176

Bravo AF: 0.183

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.78
CADD	Benign	7.6
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9860885; hg19: chr3-45430245;