chr5-168486598-C-T

Position:

• chr5-168486598-C-T

Variant summary

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

The NM_002887.4(RARS1):​c.45+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,540,754 control chromosomes in the GnomAD database, including 129,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18720 hom., cov: 32)
  • Exomes 𝑓: 0.39 (110471 hom.)
• Consequence: RARS1 NM_002887.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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=-0.76).
• BP6: Variant 5-168486598-C-T is Benign according to our data. Variant chr5-168486598-C-T is described in ClinVar as [Benign]. Clinvar id is 1243311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARS1	NM_002887.4	c.45+55C>T		intron_variant		ENST00000231572.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARS1	ENST00000231572.8	c.45+55C>T		intron_variant		1	NM_002887.4	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72315 AN: 151886 Hom.: 18677 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.389 AC: 540114 AN: 1388750 Hom.: 110471 AF XY: 0.388 AC XY: 265929 AN XY: 685622

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.476 AC: 72407 AN: 152004 Hom.: 18720 Cov.: 32 AF XY: 0.482 AC XY: 35790 AN XY: 74284

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.473

Alfa AF: 0.376 Hom.: 14460

Bravo AF: 0.507

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.3
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193466; hg19: chr5-167913603;