3-45485503-G-A

Position:

• chr3-45485503-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.1019-189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 152,230 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.018 (72 hom., cov: 33)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.117

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]

LARS2-AS1 (HGNC:40796): (LARS2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-45485503-G-A is Benign according to our data. Variant chr3-45485503-G-A is described in ClinVar as [Benign]. Clinvar id is 1243776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARS2	NM_015340.4	c.1019-189G>A		intron_variant		ENST00000645846.2
LARS2-AS1	NR_048543.1	n.518-1472C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARS2	ENST00000645846.2	c.1019-189G>A		intron_variant			NM_015340.4	P1
LARS2-AS1	ENST00000442534.2	n.518-1472C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2700 AN: 152112 Hom.: 71 Cov.: 33

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0179 AC: 2718 AN: 152230 Hom.: 72 Cov.: 33 AF XY: 0.0176 AC XY: 1312 AN XY: 74428

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.000479 Hom.: 1

Bravo AF: 0.0203

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	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.42

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: rs9842998; hg19: chr3-45526995;