rs193466

Variant names:

• chr5-168486598-C-T
• rs193466
• NM_002887.4:c.45+55C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-168486598-C-T
• chr5-168486598-C-A
• chr5-168486598-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

RARS1 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 9

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002887.4. 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
	RARS1	NM_002887.4	MANE Select	c.45+55C>T		intron	N/A	NP_002878.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARS1	ENST00000231572.8	TSL:1 MANE Select	c.45+55C>T		intron	N/A	ENSP00000231572.3	P54136-1
	RARS1	ENST00000922755.1		c.45+55C>T		intron	N/A	ENSP00000592814.1
	RARS1	ENST00000953515.1		c.45+55C>T		intron	N/A	ENSP00000623574.1

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

African (AFR) AF: 0.656 AC: 20624 AN: 31440

American (AMR) AF: 0.646 AC: 23029 AN: 35650

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8432 AN: 25110

East Asian (EAS) AF: 0.711 AC: 25395 AN: 35708

South Asian (SAS) AF: 0.415 AC: 32817 AN: 79026

European-Finnish (FIN) AF: 0.369 AC: 17171 AN: 46494

Middle Eastern (MID) AF: 0.515 AC: 2877 AN: 5586

European-Non Finnish (NFE) AF: 0.359 AC: 385385 AN: 1072040

Other (OTH) AF: 0.423 AC: 24384 AN: 57696

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

African (AFR) AF: 0.647 AC: 26821 AN: 41438

American (AMR) AF: 0.567 AC: 8670 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3466

East Asian (EAS) AF: 0.718 AC: 3699 AN: 5152

South Asian (SAS) AF: 0.423 AC: 2041 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3969 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24597 AN: 67968

Other (OTH) AF: 0.473 AC: 995 AN: 2104

Alfa AF: 0.391 Hom.: 20081

Bravo AF: 0.507

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.3
DANN	Benign	0.89
PhyloP100		-1.8
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs193466; hg19: chr5-167913603;