ENST00000524082.5:n.4C>A

Variant names:

• chr5-168486454-C-A
• rs2305725
• ENST00000524082.5:n.4C>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000524082.5(RARS1):​n.4C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,544,498 control chromosomes in the GnomAD database, including 23,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1728 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21976 hom.)
• Consequence: RARS1 ENST00000524082.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.99

Genes affected

RARS1 (HGNC:9870): (arginyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Arginyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-168486454-C-A is Benign according to our data. Variant chr5-168486454-C-A is described in ClinVar as [Benign]. Clinvar id is 380049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS1	NM_002887.4	c.-45C>A		upstream_gene_variant		ENST00000231572.8	NP_002878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS1	ENST00000231572.8	c.-45C>A		upstream_gene_variant		1	NM_002887.4	ENSP00000231572.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19811 AN: 152092 Hom.: 1727 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.129 AC: 20248 AN: 157266 Hom.: 1640 AF XY: 0.129 AC XY: 10656 AN XY: 82728

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.0726

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0528

Gnomad SAS exome AF: 0.0626

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.171 AC: 238522 AN: 1392288 Hom.: 21976 Cov.: 28 AF XY: 0.169 AC XY: 115896 AN XY: 687188

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.0774

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0643

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.130 AC: 19811 AN: 152210 Hom.: 1728 Cov.: 32 AF XY: 0.127 AC XY: 9456 AN XY: 74408

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.121

Alfa AF: 0.162 Hom.: 1899

Bravo AF: 0.119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.50
DANN	Benign	0.81

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: rs2305725; hg19: chr5-167913459; COSMIC: COSV51563584; COSMIC: COSV51563584;