rs9842998

Variant names:

• chr3-45485503-G-A
• rs9842998
• NM_015340.4:c.1019-189G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-45485503-G-A
• chr3-45485503-G-C
• chr3-45485503-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015340.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS2	NM_015340.4	MANE Select	c.1019-189G>A		intron	N/A	NP_056155.1	Q15031
	LARS2	NM_001368263.1		c.1019-189G>A		intron	N/A	NP_001355192.1	Q15031
	LARS2-AS1	NR_048543.1		n.518-1472C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS2	ENST00000645846.2	MANE Select	c.1019-189G>A		intron	N/A	ENSP00000495093.1	Q15031
	LARS2	ENST00000265537.8	TSL:1	n.1019-189G>A		intron	N/A	ENSP00000265537.4	A0A499FJL2
	LARS2	ENST00000935381.1		c.1019-189G>A		intron	N/A	ENSP00000605440.1

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

African (AFR) AF: 0.0581 AC: 2415 AN: 41560

American (AMR) AF: 0.0100 AC: 153 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 65 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68014

Other (OTH) AF: 0.0185 AC: 39 AN: 2108

Alfa AF: 0.00587 Hom.: 6

Bravo AF: 0.0203

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs9842998; hg19: chr3-45526995;