chr3-45388659-G-A

Position:

• chr3-45388659-G-A

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.-109G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,256 control chromosomes in the GnomAD database, including 4,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4596 hom., cov: 32)
  • Exomes 𝑓: 0.29 (4 hom.)
• Consequence: LARS2 NM_015340.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.18

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=-0.58).
• BP6: Variant 3-45388659-G-A is Benign according to our data. Variant chr3-45388659-G-A is described in ClinVar as [Benign]. Clinvar id is 1294389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.-109G>A		5_prime_UTR_variant	1/22	ENST00000645846.2	NP_056155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2	c.-109G>A		5_prime_UTR_variant	1/22		NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34754 AN: 152076 Hom.: 4595 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.290 AC: 18 AN: 62 Hom.: 4 Cov.: 0 AF XY: 0.325 AC XY: 13 AN XY: 40

Gnomad4 AFR exome AF: 0.250

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.228 AC: 34756 AN: 152194 Hom.: 4596 Cov.: 32 AF XY: 0.232 AC XY: 17275 AN XY: 74404

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.206

Alfa AF: 0.261 Hom.: 2199

Bravo AF: 0.204

Asia WGS AF: 0.128 AC: 444 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	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs28413188; hg19: chr3-45430151;