rs2071101

Positions:

• chr11-3028907-C-T

Variant summary

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

The NM_001014437.3(CARS1):​c.1031+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 908,756 control chromosomes in the GnomAD database, including 4,630 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 0.025 (533 hom., cov: 32)
  • Exomes 𝑓: 0.033 (4097 hom.)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARS1	NM_001014437.3	c.1031+89G>A		intron_variant		ENST00000380525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARS1	ENST00000380525.9	c.1031+89G>A		intron_variant		1	NM_001014437.3	P3

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3783 AN: 152164 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.00417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0330 AC: 24941 AN: 756474 Hom.: 4097 Cov.: 10 AF XY: 0.0324 AC XY: 12909 AN XY: 398478

Gnomad4 AFR exome AF: 0.00349

Gnomad4 AMR exome AF: 0.0924

Gnomad4 ASJ exome AF: 0.00291

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.000332

Gnomad4 NFE exome AF: 0.00163

Gnomad4 OTH exome AF: 0.0341

GnomAD4 genome AF: 0.0249 AC: 3785 AN: 152282 Hom.: 533 Cov.: 32 AF XY: 0.0280 AC XY: 2084 AN XY: 74456

Gnomad4 AFR AF: 0.00416

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.00821 Hom.: 8

Bravo AF: 0.0304

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.2
DANN	Benign	0.86

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: rs2071101; hg19: chr11-3050137; COSMIC: COSV53450338; COSMIC: COSV53450338;