rs2305737

Positions:

• chr5-168519256-C-A
• chr5-168519256-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000231572.8(RARS1):​c.*66C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,253,058 control chromosomes in the GnomAD database, including 2,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.043 (444 hom., cov: 32)
  • Exomes 𝑓: 0.027 (2002 hom.)
• Consequence: RARS1 ENST00000231572.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARS1	NM_002887.4	c.*66C>A		3_prime_UTR_variant	15/15	ENST00000231572.8	NP_002878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARS1	ENST00000231572.8	c.*66C>A		3_prime_UTR_variant	15/15	1	NM_002887.4	ENSP00000231572	P1
RARS1	ENST00000520013.5	c.*1550C>A		3_prime_UTR_variant, NMD_transcript_variant	14/14	2		ENSP00000429030

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6536 AN: 152080 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0415

GnomAD4 exome AF: 0.0272 AC: 29891 AN: 1100858 Hom.: 2002 Cov.: 14 AF XY: 0.0258 AC XY: 14392 AN XY: 557344

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.0433

Gnomad4 NFE exome AF: 0.00974

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.0431 AC: 6553 AN: 152200 Hom.: 444 Cov.: 32 AF XY: 0.0479 AC XY: 3566 AN XY: 74414

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0201 Hom.: 174

Bravo AF: 0.0557

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.74

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: rs2305737; hg19: chr5-167946261; COSMIC: COSV51563672;