chr3-45391634-G-A

Position:

• chr3-45391634-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.-36G>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 0.0402 in 151,804 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (153 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LARS2 NM_015340.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.328

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=-0.97).
• BP6: Variant 3-45391634-G-A is Benign according to our data. Variant chr3-45391634-G-A is described in ClinVar as [Benign]. Clinvar id is 380550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.-36G>A		5_prime_UTR_variant	2/22	ENST00000645846.2	NP_056155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2	c.-36G>A		5_prime_UTR_variant	2/22		NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6097 AN: 151684 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0354

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0402 AC: 6102 AN: 151804 Hom.: 153 Cov.: 32 AF XY: 0.0407 AC XY: 3022 AN XY: 74176

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0376 Hom.: 28

Bravo AF: 0.0399

Asia WGS AF: 0.0890 AC: 309 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

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	-0.97
CADD	Benign	2.0
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs75054661; hg19: chr3-45433126;