rs1058751

Positions:

• chr9-92210634-T-A

Variant summary

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

The NM_002161.6(IARS1):​c.*173A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 560,654 control chromosomes in the GnomAD database, including 4,894 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 0.11 (1104 hom., cov: 33)
  • Exomes 𝑓: 0.13 (3790 hom.)
• Consequence: IARS1 NM_002161.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

Genes affected

IARS1 (HGNC:5330): (isoleucyl-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. Isoleucine-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family and has been identified as a target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IARS1	NM_002161.6	c.*173A>T		3_prime_UTR_variant	34/34	ENST00000443024.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IARS1	ENST00000443024.7	c.*173A>T		3_prime_UTR_variant	34/34	5	NM_002161.6	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17084 AN: 152120 Hom.: 1100 Cov.: 33

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.127 AC: 51900 AN: 408416 Hom.: 3790 Cov.: 3 AF XY: 0.132 AC XY: 28099 AN XY: 213442

Gnomad4 AFR exome AF: 0.0638

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.0564

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.112 AC: 17102 AN: 152238 Hom.: 1104 Cov.: 33 AF XY: 0.117 AC XY: 8740 AN XY: 74422

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0776

Gnomad4 EAS AF: 0.0653

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.112

Alfa AF: 0.119 Hom.: 148

Bravo AF: 0.108

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1058751; hg19: chr9-94972916; COSMIC: COSV65116796; COSMIC: COSV65116796;