rs406598

Positions:

• chr11-3055055-G-A
• chr11-3055055-G-T

Variant summary

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

The NM_001014437.3(CARS1):​c.25+2288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 673,380 control chromosomes in the GnomAD database, including 56,769 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 0.33 (10234 hom., cov: 34)
  • Exomes 𝑓: 0.41 (46535 hom.)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

Genes affected

CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARS1	NM_001014437.3	c.25+2288C>T		intron_variant		ENST00000380525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARS1	ENST00000380525.9	c.25+2288C>T		intron_variant		1	NM_001014437.3	P3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49756 AN: 152052 Hom.: 10226 Cov.: 34

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.410 AC: 213936 AN: 521210 Hom.: 46535 Cov.: 0 AF XY: 0.411 AC XY: 115996 AN XY: 282410

Gnomad4 AFR exome AF: 0.0804

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.327 AC: 49772 AN: 152170 Hom.: 10234 Cov.: 34 AF XY: 0.329 AC XY: 24499 AN XY: 74376

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.355

Alfa AF: 0.342 Hom.: 1576

Bravo AF: 0.329

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.57

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: rs406598; hg19: chr11-3076285;