3-45485607-C-G

Variant names:

• chr3-45485607-C-G
• rs7640603
• NM_015340.4:c.1019-85C>G

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.1019-85C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 730,388 control chromosomes in the GnomAD database, including 341,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (61946 hom., cov: 32)
  • Exomes 𝑓: 0.98 (279558 hom.)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324
• Publications: 3 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=-0.78).
• BP6: Variant 3-45485607-C-G is Benign according to our data. Variant chr3-45485607-C-G is described in ClinVar as Benign. ClinVar VariationId is 676142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 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.1019-85C>G		intron	N/A	NP_056155.1	Q15031
	LARS2	NM_001368263.1		c.1019-85C>G		intron	N/A	NP_001355192.1	Q15031
	LARS2-AS1	NR_048543.1		n.518-1576G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS2	ENST00000645846.2	MANE Select	c.1019-85C>G		intron	N/A	ENSP00000495093.1	Q15031
	LARS2	ENST00000265537.8	TSL:1	n.1019-85C>G		intron	N/A	ENSP00000265537.4	A0A499FJL2
	LARS2	ENST00000935381.1		c.1019-85C>G		intron	N/A	ENSP00000605440.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134756 AN: 152118 Hom.: 61907 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.958

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.910

GnomAD4 exome AF: 0.981 AC: 567068 AN: 578152 Hom.: 279558 AF XY: 0.982 AC XY: 298237 AN XY: 303758

African (AFR) AF: 0.588 AC: 9633 AN: 16376

American (AMR) AF: 0.970 AC: 22179 AN: 22864

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 14289 AN: 14360

East Asian (EAS) AF: 1.00 AC: 32556 AN: 32564

South Asian (SAS) AF: 0.962 AC: 41666 AN: 43322

European-Finnish (FIN) AF: 1.00 AC: 46347 AN: 46348

Middle Eastern (MID) AF: 0.971 AC: 3606 AN: 3712

European-Non Finnish (NFE) AF: 0.998 AC: 368486 AN: 369270

Other (OTH) AF: 0.965 AC: 28306 AN: 29336

GnomAD4 genome AF: 0.886 AC: 134853 AN: 152236 Hom.: 61946 Cov.: 32 AF XY: 0.889 AC XY: 66216 AN XY: 74452

African (AFR) AF: 0.612 AC: 25359 AN: 41456

American (AMR) AF: 0.953 AC: 14581 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.958 AC: 4626 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67880 AN: 68040

Other (OTH) AF: 0.911 AC: 1928 AN: 2116

Alfa AF: 0.932 Hom.: 7949

Bravo AF: 0.868

Asia WGS AF: 0.960 AC: 3338 AN: 3478

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	-0.78
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs7640603; hg19: chr3-45527099;